Comparison of Efficacy and Tolerability of Two Cough Syrups in Cough Due to Cold in Children.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Comparison of Efficacy and Tolerability of Two Cough Syrups in Cough Due to Cold in Children. (NCT01968434), a randomized phase 4 study. The primary outcome is Change in Night Cough Score on First Night of Treatment (From N0 to N1).

2. Clinical Question

The study’s rationale focused on cough frequency and intensity, disturbance from night cough, and the child’s sleep. The brief summary frames the comparison as whether the protective syrup relieves cough at least as much as carbocisteine, while avoiding suppression of the cough reflex. That framing describes the research question; it is not itself evidence that either treatment has a particular clinical effect.

The posted primary outcome is a continuous score based on parent ratings of five aspects of night cough. The main comparison is therefore a difference in average score change, rather than a count of children who met a threshold for response. The registry record does not report a threshold defining a clinically important change or an equivalence margin. Consequently, the results can describe the observed score differences and their statistical precision, but cannot establish equivalence or tell whether the difference meets a particular clinical-importance standard.

3. Trial Design

The registry record identifies NCT01968434 as a phase 4, randomized, single-blind, multicenter, parallel-group study. It compared a protective cough syrup with carbocisteine cough syrup in children with cough due to upper respiratory tract infection. The sponsor was Clalit Health Services. The record lists the study as completed, with a start in 2013-12 and primary completion in 2014-03.

The registry reports enrollment of 150. The primary outcome analysis description says that the analyzed population consisted of children who completed the protocol and submitted complete questionnaires for night and day cough. It reports 78 enrolled in the protective syrup group and 72 in the carbocysteine group; the primary outcome results use 75 and 66 participants, respectively. The record does not fully explain the differences between the enrolled and analyzed counts. It also does not report the randomization procedure, allocation concealment, the identity of the party blinded, or how blinding was maintained. Those details are not reported in the registry record.

The primary endpoint was measured from the night before enrollment to the first night after treatment. Secondary outcomes concerned change in night and day cough scores at the end of the study, described as 4 nights and 3 days. The intervention descriptions give a duration of 4 nights and 3 days. The posted outcome results include fewer analyzed participants than the enrollment count, with analysis numbers differing by outcome. This makes it important to distinguish enrollment from the numbers contributing to each reported result.

The registry record does not report the original sample-size justification, a prespecified statistical analysis plan, or whether analyses were conducted on an intention-to-treat basis. It also does not describe a formal equivalence or non-inferiority design. The comparative results should therefore be read as the registry’s reported between-group analysis and a simple unadjusted recalculation, not as evidence that a particular design objective was established.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: Access for eligibility= 195 Excluded =45 (refused to participate n= 24, not meeting inclusion criteria n=21)

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: the population analyzed are the children who completed the protocol and submitted the complete questionnaire for night and day cough. 78 patients were enrolled in the protective syrup Group and 72 in the carbocysteine Group. 3 patients in the protective syrup group and 6 in the carbocysteine group never began the study.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Enrolled patients had a minimum cough intensity both day and night, according to questionnaire, had not received any cough medicine the day before enrollment and fulfilled all inclusion criteria.

6. Primary Endpoint

The registry lists the primary outcome as Change in Night Cough Score on First Night of Treatment (From N0 to N1), measured over 1 night from before enrollment (N0) to first night after treatment (N1).

The primary endpoint is change in the combined night cough score from N0, the night before enrollment, to N1, the first night after treatment. Parents rated five aspects: cough frequency, severity, bothersomeness, child sleep, and parent sleep. Each aspect used a 7 point Likert scale from 0 (not at all) to 6 (extremely). The ratings were added to form a combined score ranging from 0-30. The score at N1 was compared with the baseline score at N0.

Lower scores indicate a better condition, so a negative change represents improvement. The endpoint was chosen to capture night cough and its effects on both child and parent sleep, which the registry description identifies as especially bothersome. Combining the five ratings gives a single continuous measure that can be compared between groups as an average change.

This measure is based on parental assessment, not an objective count of cough events. The registry record describes the questionnaire as validated, but does not report its validation details, a minimum clinically important difference, or a threshold for classifying a child as improved. Interpretation therefore rests on the direction and size of the average score changes, together with the uncertainty around the between-group contrast. The score alone does not establish whether a measured difference is important to families in practical terms.

7. Results Posted in the Registry

• Carbocisteine Cough Syrup: mean -1.77 versus -5.16 on control; difference 3.39 (95% CI 1.27 to 5.51), standardized effect d = 0.52; z-test p = 0.002.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Change in Night Cough Score at End of Study (From N0 to N4)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Carbocisteine Cough Syrup: mean -9.48 versus -13.92 on control; difference 4.44 (95% CI 1.66 to 7.22), standardized effect d = 0.55; z-test p = 0.002.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Carbocisteine Cough Syrup than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change in Day Cough Score at End of Study (From D0 to D4)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Carbocisteine Cough Syrup: mean -4.54 versus -6.17 on control; difference 1.63 (95% CI 0.18 to 3.08), standardized effect d = 0.39; z-test p = 0.027.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Carbocisteine Cough Syrup than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes extend the comparison beyond the first night to night cough and day cough at the end of the study. Across these outcomes, the posted mean changes are more negative in the protective syrup group, in keeping with the direction of the primary comparison. The registry reports a two-sided test for each secondary endpoint, with p <0.01 for end-of-study night cough and p <0.05 for end-of-study day cough.

This overall pattern is consistent with, but does not independently settle, the primary result. Secondary outcomes can provide supporting context because they address related measures over a longer period and during the day as well as at night. They are not interchangeable with the primary endpoint: the time points and score measures differ, and the primary question was defined around the first night after treatment.

The registry record does not report whether secondary outcomes were prespecified in a statistical analysis plan, whether a hierarchy was used, or whether multiplicity adjustment was applied. When several outcomes are tested, the chance of finding at least one apparently notable result can increase. Unadjusted secondary p-values therefore carry less confirmatory weight than a single prespecified primary test, particularly when their testing relationship is not described. The directionally consistent pattern is informative descriptively, but should not be treated as a set of independent confirmations.

The analysis numbers also differ by endpoint, and the record describes the primary analysis population as children with completed protocol and complete questionnaires. Without fuller information about missing data, the consistency of the endpoint pattern cannot rule out the possibility that analyzed participants differed from those without available results. The secondary findings add context to the observed score changes, while the missing analysis details limit the strength of conclusions drawn from them.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Change in Night Cough Score at End of Study (From N0 to N4)
• Change in Day Cough Score at End of Study (From D0 to D4)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it is a numerical score, and the reported group summaries are means with standard errors. A mean describes the average score change among analyzed participants. The standard error describes the uncertainty in the estimated mean, rather than the spread of individual participants’ scores. It should not be read as a range containing most individual changes. The registry does not post standard deviations for this endpoint; the summary figures list standard errors.

What does the between-group estimate mean?

The recalculated mean difference is 3.39, defined as the carbocisteine group’s mean change minus the protective syrup group’s mean change. Since decreases in the score indicate improvement, a positive value for this particular subtraction means the protective syrup group had the more negative average change. This direction depends on the subtraction order. A mean difference has the same units as the outcome, so the estimate is expressed in change in combined night cough score, not as a percentage or a relative risk.

The recalculation uses the posted group means and standard errors and is an unadjusted comparison. It does not account for baseline score differences, center, or other covariates. The registry reports a two-sided t-test. A two-sided test evaluates evidence for a difference in either direction, rather than only testing whether one named group is better. The registry’s primary p-value is reported as <0.01; the unadjusted recalculation gives 0.002. The registry record does not report the test statistic or enough information to reconstruct every detail of the sponsor’s analysis.

How should a p-value be understood?

In general, a p-value describes how surprising data at least as incompatible with a specified no-difference model would be, if that model and the test assumptions held. It is not the probability that the no-difference model is true, and it is not a measure of clinical importance. A small p-value does not quantify how likely the result is to replicate. It also does not address bias from missing data, outcome measurement, or study conduct.

The registry presents a test result for the primary endpoint and for each of the two secondary outcomes. The record does not say whether the analyses were prespecified in a statistical analysis plan or adjusted for testing multiple outcomes. Without that information, p-values across several outcomes should not all be treated as independent confirmatory findings. Testing multiple hypotheses can increase the chance of at least one apparently notable result, which is why a prespecified testing hierarchy or multiplicity adjustment may be used in general. Whether either approach was used in this study is not reported in the registry record.

Why might over-dispersion matter?

General explanation: over-dispersion occurs when observations vary more than a statistical model assumes. It is especially relevant to count outcomes, where an overly simple model can understate uncertainty if participants or settings differ more than expected. The primary endpoint is a continuous parent-rated score, and the registry reports a t-test; the record does not report an over-dispersion assessment or a model that addresses it. The issue should not be assumed to have affected this analysis. More generally, the suitability of a statistical test depends on its assumptions and on how the outcome data are distributed.

The posted confidence interval for the recalculated mean difference is 1.269 to 5.511. A confidence interval is a range of values compatible with the observed data under a specified method. In repeated use of a method, intervals constructed at a stated confidence level would cover the underlying parameter at that level. The registry record does not report the confidence level for this recalculated interval, so no level should be attributed to it. A wider interval indicates less precision than a narrower interval, while the interval’s position relative to no difference helps describe statistical compatibility.

The reported analysis population matters as well. The primary outcome description says the analysis included children who completed the protocol and submitted complete questionnaires. This is a completed-questionnaire analysis population, not necessarily everyone randomized. The record does not report the analysis population definition in enough detail to determine how withdrawals, incomplete forms, or other missing outcomes were handled. In general, excluding participants with missing outcomes can affect the comparison if missingness is related to treatment or outcome.

The difference between a reported analysis and a recalculation should remain clear. The registry analysis is the sponsor’s posted test result. The recalculation derives a simple unadjusted comparison from group-level summary statistics. It can provide a useful check on scale and direction, but cannot reproduce unreported adjustments, data-handling decisions, or analysis details. Since no discrepancy is flagged, the registry’s own analysis remains the primary account of the sponsor’s inferential result.

11. Confidence Intervals and Precision

The recalculated primary mean difference is 3.39, with an interval from 1.269 to 5.511. The contrast is expressed as carbocisteine minus protective syrup, so the positive direction corresponds to a more negative, and therefore more favorable, average score change in the protective syrup group. The interval does not include no difference. This is consistent with the reported primary test result, p <0.01, and the unadjusted recalculated p-value of 0.002.

The interval communicates uncertainty about the estimated average contrast; it does not show the range of individual children’s responses. Its span also means the exact size of the group difference is not pinned down to a single value. The registry record does not specify the confidence level for the recalculated interval, so its nominal coverage level is not reported in the registry record. The sponsor’s reported primary result gives a p-value but does not include an interval or an exact estimate in the reported analysis.

Precision depends on the amount of information in the analysis, variability in scores, and the analysis method. The group summaries report standard errors of 0.85 and 0.67, and the primary analysis numbers are 75 and 66. The registry record does not report the distribution of individual changes, the proportion with missing outcome data by reason, or adjusted estimates that could add context to precision. An interval can describe statistical uncertainty under its method, but it cannot account for biases that the method does not model.

The interval is not a clinical-importance threshold. The record does not report a minimum important difference for the combined night cough score, so it is not possible to determine from the interval alone whether its values correspond to small or meaningful changes for children and families. Statistical precision and clinical interpretation are related but distinct: the first concerns uncertainty in an estimated contrast, while the second requires a defensible standard for what change matters.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size illustrations are planning calculations based on the observed effect, not the trial’s original design calculations. They assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to a stated fraction of the observed effect. The figures are participants per arm for these continuous outcomes; they are not total event counts.

The column for 80% power gives the number of participants per arm that the calculation estimates would be needed for an 80% chance of detecting the specified effect under those assumptions, if the assumed effect and model were correct. The 90% power column uses the higher target probability of detecting that effect and therefore generally calls for more participants per arm. These are design-planning concepts, not probabilities that the observed study result is correct.

Each planning row uses a different fraction of the observed effect. Planning for 75% of the observed effect requires more participants than planning for 100% of the observed effect; planning for 50% requires still more. This pattern is expected: smaller effects are harder to distinguish from random variation, so detecting them with the same target power generally requires a larger sample. For the primary endpoint, the posted illustrations give 59 and 79 participants per arm for planning for 100% of the observed effect at 80% and 90% power, respectively; the corresponding figures for planning for 75% are 104 and 139, and for planning for 50% are 234 and 313.

These are not observed power calculations. They are planning illustrations derived from the effect estimated in this study, which can itself be imprecise. The registry record does not report the original sample-size assumptions or justification, so these illustrations should not be taken as evidence about the trial’s initial design choices.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 3.390; pooled standard deviation σ = 6.535.
2. n = 2 × (1.96 + 0.842)² × 6.535² / 3.390² = 58.3, rounded up to 59 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 3.39                      # observed difference in means
sigma <- 6.53471966889775                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1968434)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 59 (80% power), 79 (90% power)
 75% of observed effect: n per arm = 104 (80% power), 139 (90% power)
 50% of observed effect: n per arm = 234 (80% power), 313 (90% power)
power.t.test: 59.3 
Simulated power at n = 59 per arm: 0.801 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary analysis as a two-sided t-test with p <0.01. It does not report the sponsor’s exact mean difference, confidence interval, test statistic, or exact p-value. For the secondary outcomes, the registry also reports two-sided t-tests, with p <0.01 for night cough at the end of the study and p <0.05 for day cough at the end of the study.

The recalculated primary comparison uses the posted group means and standard errors to give an unadjusted mean difference of 3.39, an interval from 1.269 to 5.511, and p = 0.002. This is a simple check based on summary statistics; it does not reproduce possible adjustments or data-handling decisions that are not described in the registry record. The sponsor’s own analysis takes precedence as the reported trial analysis. In this case, the registry flags no discrepancy between the posted result and the recalculation.

The recalculation can help explain the size and direction of the primary contrast, but it does not replace the sponsor’s analysis or fill in unreported methods. The registry’s threshold p-value and the recalculated value are different forms of reporting rather than evidence of a contradiction.

15. Multiplicity, Missing Data and Analysis Populations

The registry record reports one primary endpoint and two secondary outcomes, each with a two-sided test. It does not report a multiplicity adjustment, a hierarchy of hypotheses, or a statistical analysis plan describing how the family of tests was to be interpreted. The primary result is therefore the clearest inferential focus in the record. Secondary p-values should be treated as less conclusive because several outcomes were tested and the record does not explain how that multiplicity was handled.

The primary outcome description defines the analyzed population as children who completed the protocol and submitted complete night and day cough questionnaires. The record gives group enrollment counts of 78 and 72, while the primary outcome results report analysis numbers of 75 and 66. It does not fully explain the difference between enrollment and analysis counts. The end-of-study secondary outcomes have their own analysis numbers, which also vary by outcome. Reasons for missing questionnaires, withdrawals, or exclusion are not reported in the registry record.

These details matter because an analysis limited to participants with complete outcomes can be biased if the likelihood of having a complete questionnaire is associated with treatment assignment or cough outcome. The registry record does not report whether missing outcomes were imputed, whether sensitivity analyses were conducted, or whether participants were analyzed according to randomized assignment. An intention-to-treat analysis population is not reported in the registry record.

The record also does not report baseline outcome values by group, the allocation concealment procedure, the blinding details, or whether the analysis adjusted for baseline scores or study center. These omissions do not establish that a problem occurred; they limit how fully the reported analysis can be evaluated. In particular, the available group summaries do not show whether the groups had comparable baseline cough scores or how any baseline imbalance was addressed.

As a result, the posted p-values and recalculated intervals describe statistical comparisons for the reported analyzed participants, under their respective methods. They do not address uncertainty from unreported missing-data handling or multiplicity procedures. A complete statistical interpretation would require the analysis plan and fuller participant-flow and missing-outcome information, which are not reported in the registry record.

16. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports zero serious adverse events among 75 participants at risk in the protective cough syrup group and zero among 66 at risk in the carbocisteine group. These figures describe the serious adverse event counts recorded for the stated risk groups during the study; they do not establish that serious events cannot occur or that the treatments have identical safety profiles.

Other adverse events are reported for 6 participants at risk in the protective syrup group and 9 in the carbocisteine group. These are counts, not a complete account of event types or severity. The registry record does not list serious adverse event terms, and deaths are not reported in the registry record. It also does not provide the timing, duration, relatedness assessments, or detailed descriptions of the other adverse events.

Safety comparisons are limited by the study’s size and duration, described as 4 nights and 3 days. A count of zero serious events in the posted results is not proof of no risk, particularly when the observation period is short. The adverse-event figures should be read as the events recorded in this trial, not as a complete estimate of safety across broader use.

17. What the Result Does, and Does Not, Mean

The posted primary results show a more negative average change in the combined night cough score in the protective syrup group than in the carbocisteine group after the first night. Under the score definition, a more negative change indicates a greater reduction in the score. The registry’s two-sided primary test is reported as p <0.01, and the unadjusted recalculation also indicates a difference, with a mean contrast of 3.39 and an interval from 1.269 to 5.511.

These findings describe the analyzed participants and the score measured by the study. They do not establish that one treatment is clinically superior for every child, prove a particular mechanism, or show that a difference is meaningful to families. The record does not report a threshold for clinical importance, and the study summary’s hypothesis that the protective syrup could relieve cough as much as or more than carbocisteine is not the same as a formal equivalence or non-inferiority conclusion.

The study was randomized and single blind according to the registry, but additional design details are not reported. The outcome relied on parent ratings, and the record’s primary analysis population consists of children with complete questionnaires. Missing-data handling and the analysis population’s relationship to random assignment are not fully described. These limitations affect how confidently the observed results can be generalized beyond the analyzed participants.

The secondary results show a similar overall direction for end-of-study cough scores, but multiple testing procedures are not reported. They provide supportive descriptive context rather than a reason to disregard the primary endpoint’s limitations. The safety results report no serious adverse events in either group in the posted risk groups, but other adverse events were recorded, and the study’s brief duration and incomplete event detail limit what can be concluded about safety.

Overall, the registry describes a statistically notable difference in average parent-rated cough score change, with the protective syrup group showing the more favorable direction under the scoring convention. The evidence does not resolve clinical importance, long-term outcomes, or questions beyond the specific population, outcomes, and observation period recorded in this trial.

18. Why This Trial Matters Statistically

This trial illustrates why a treatment comparison needs more than a p-value. The primary outcome is a composite parent-rated score, and the observed group means communicate the direction of change. The between-group estimate and its interval add information about the size and precision of the average contrast. A p-value alone would not show that the direction of the score is favorable, or how uncertain the estimated difference is.

It also demonstrates the importance of distinguishing a reported sponsor analysis from a recalculation based on summary statistics. The registry reports a two-sided test with p <0.01; an unadjusted recalculation gives p = 0.002 and an interval for the mean contrast. The recalculation is informative but cannot reproduce analysis choices that are not reported. Where the two accounts are consistent, the recalculation can clarify scale and direction without replacing the sponsor’s own analysis.

Sample-size illustrations based on an observed effect show why planning for a smaller effect calls for more participants. They can help readers understand the relationship between effect size and precision, but they are not the trial’s original design justification and are not observed power. The record does not report the original planning assumptions, so the illustrations cannot be used to infer what the investigators intended to detect.

Finally, the variation in analysis numbers across outcomes and the limited description of missing data show why participant flow is part of statistical interpretation. Randomization does not by itself explain how incomplete outcomes were handled. Multiplicity and analysis-population details are likewise necessary to judge how much weight secondary findings should carry. Together, these considerations make this study a useful example of interpreting effect estimates, uncertainty, and reporting limitations as complementary parts of the evidence.

19. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several trial-specific limitations follow from the registry record. The primary endpoint is based on parents’ ratings of five cough-related aspects, including child and parent sleep. Although the record calls the questionnaire validated, it does not report validation details, measurement properties in this study, or a threshold for a clinically important difference. The outcome is therefore interpretable as a score change, but its practical importance cannot be determined from the record alone.

The primary results are reported for 75 participants in the protective syrup group and 66 in the carbocisteine group, while the outcome description reports enrollment of 78 and 72. The record does not fully explain this difference. The secondary outcomes use other analysis numbers, and reasons for missing or unavailable outcomes are not reported. This leaves uncertainty about selection into the analyzed population and the possible effect of missing data.

The record identifies the study as single blind but does not identify who was blinded or explain how blinding was maintained. Because the primary endpoint relies on parent ratings, unreported blinding details are relevant to interpretation. Randomization procedure and allocation concealment are also not described. These omissions do not establish that bias occurred, but prevent a full assessment of how treatment assignment and outcome assessment were protected from bias.

The original sample-size justification, analysis plan, multiplicity strategy, and missing-data procedures are not reported in the registry record. The record does not give an equivalence margin or a clinically important score threshold. The study’s stated course was short, and the safety record lacks detailed event descriptions and reports no deaths. Consequently, the results are limited to the recorded outcomes and observation period and do not provide a detailed assessment of longer-term effects or safety.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Comparison of Efficacy and Tolerability of Two Cough Syrups in Cough Due to Cold in Children. — NCT01968434.
• Registry record last updated 2018-02-23; status last verified 2018-01.
• Results first posted 2015-11-02.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

23. Record Summary

NCT01968434 is a completed, phase 4, randomized, single-blind, multicenter, parallel-group study sponsored by Clalit Health Services. It enrolled 150 children with cough due to upper respiratory tract infection and compared a protective syrup with carbocisteine syrup. The primary outcome was change in the combined night cough score from the night before enrollment to the first night after treatment.

The protective syrup group had a mean primary score change of -5.16, compared with -1.77 in the carbocisteine group. The registry reports p <0.01 for the primary test; an unadjusted recalculation gives a mean difference of 3.39, an interval from 1.269 to 5.511, and p = 0.002. The secondary outcomes show a similar overall direction, though multiplicity procedures are not reported. Serious adverse event counts were zero in both groups; other adverse events were recorded in both. Missing-data handling, original sample-size justification, and several analysis details are not reported in the registry record.