Effectiveness of Low-Dose Theophylline for the Management of Biomass-Associated COPD: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effectiveness of Low-Dose Theophylline for the Management of Biomass-Associated COPD (NCT03984188), a randomized phase 3 study. The primary outcome is Change in St. George Respiratory Questionnaire (SGRQ) Scores.

2. Clinical Question

The study addresses a treatment question in people whose COPD is associated with household air pollution from biomass fuels. The registry summary explains that biomass-related COPD may have a distinct disease profile from tobacco-mediated COPD and describes uncertainty about the effectiveness of pharmacotherapy for this population. The study's stated aims also include respiratory symptoms, serum biomarkers, lung function, and cost-effectiveness, but the primary endpoint posted in the results is SGRQ score change.

The posted primary comparison is a mean difference between the low-dose theophylline and placebo groups. It therefore describes the average difference in the measured outcome, rather than the response of every participant or the likelihood of a particular individual outcome. The outcome is a patient-reported questionnaire score about symptoms and the functional, social, and psychological impact of disease. The primary comparison does not by itself answer the study's other stated questions about biomarkers, lung function, household air pollution effects, or costs.

3. Trial Design

The registry identifies this as a phase 3, randomized, quadruple-masked, parallel-group trial. It lists an enrollment of 100 and a completed status. The recorded study start was 2021-02-23, and primary completion was 2023-10-17. The sponsor is the University of Miami.

Participants were assigned to a low-dose theophylline group or a placebo group. Both arm descriptions include standard care; the theophylline group received low-dose theophylline in addition to standard care, while the placebo group received placebo in addition to standard care. The low-dose theophylline arm description specifies treatment over a one year period. The registry calls the study quadruple masked but does not identify in the results record which roles were masked or give further details about how masking was maintained.

The primary outcome is the change in SGRQ score, with a timeframe of baseline to one year. The posted group summaries include 39 participants in the low-dose theophylline group and 41 in the placebo group for this outcome. These are outcome-specific counts; they should not be assumed to describe every randomized participant or the analysis population for every measure. The registry does not report a detailed participant flow, reasons for missing outcome data, or a full account of the population included in each analysis.

The registry lists changes in FEV1 and FVC as secondary outcomes, as well as SGRQ at six months. It contains no reported analyses for those secondary outcomes. The registry record does not report the original sample-size justification, the planned statistical model, the protocol's full analysis plan, or details of interim analyses. Those items cannot be inferred from the posted group summaries.

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: There is a discrepancy between the protocol section enrollment number vs the participants that started in the participant flow due to one participant decided not to proceed in the study after they consented and were enrolled but left the study just prior to randomization and therefore did not proceed in the study.

Overall Study

Reasons for not completing this period:

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.

6. Primary Endpoint

The registry lists the primary outcome as Change in St. George Respiratory Questionnaire (SGRQ) Scores, measured over Baseline, 1 year.

The primary endpoint is change in the St. George Respiratory Questionnaire score from baseline to one year. The SGRQ has 50 items, with one part concerning symptoms and another concerning functional status and the social and psychological impact of disease. Its overall score ranges from 0 to 100, with higher scores indicating more limitations. Consequently, a lower score represents fewer reported limitations on this measure.

Patient-reported questionnaires are used to capture aspects of health that may not be represented fully by a physiological measure alone. The SGRQ gives a structured way to summarize patients' reported symptoms and the impact of respiratory disease on daily functioning and life. Comparing mean scores between randomized groups can describe the average difference in this reported outcome.

The registry posts group means and standard deviations for the one-year outcome and a mean difference with a confidence interval. The reported mean was 39.02 for the low-dose theophylline group and 45.06 for the placebo group. A negative mean difference is in the direction of a lower score in the theophylline group, which corresponds to fewer limitations according to the SGRQ description. The summary does not establish how individual participants changed, nor does it alone establish the cause or clinical importance of an average difference.

The registry record does not give a threshold for interpreting a clinically important SGRQ change. It also does not report further details about how the change score was calculated or whether any adjustment was made for baseline score.

7. Results Posted in the Registry

• Low-dose Theophylline Group: mean 39.02 versus 45.06 on control; difference -6.04 (95% CI -14.41 to 2.33), standardized effect d = -0.32; z-test p = 0.157.

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 Forced Expiratory Volume in One Second (FEV1)

• 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 deviations.
• Result:
  • Low-dose Theophylline Group: mean 1.40 versus 1.45 on control; difference -0.05 (95% CI -0.30 to 0.20), standardized effect d = -0.09; z-test p = 0.690.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Low-dose Theophylline Group and the control. The interval gives the range of effects that remain compatible with the data.

Change in Forced Vital Capacity (FVC)

• 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 deviations.
• Result:
  • Low-dose Theophylline Group: mean 2.47 versus 2.58 on control; difference -0.11 (95% CI -0.45 to 0.23), standardized effect d = -0.15; z-test p = 0.521.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Low-dose Theophylline Group and the control. The interval gives the range of effects that remain compatible with the data.

Change in St. George Respiratory Questionnaire (SGRQ) Scores

• 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 deviations.
• Result:
  • Low-dose Theophylline Group: mean 37.86 versus 44.45 on control; difference -6.59 (95% CI -15.12 to 1.94), standardized effect d = -0.32; z-test p = 0.130.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Low-dose Theophylline Group and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcome summaries cover lung function, measured by FEV1 and FVC, and SGRQ at six months. Across these measures, the posted mean differences are in the direction of lower values in the low-dose theophylline group, but the confidence intervals include 0. The overall pattern is therefore uncertain rather than a set of clearly separated group averages. The registry does not report analyses for the secondary outcomes.

These outcomes connect to the primary result by addressing related but distinct questions. SGRQ captures reported symptoms and the impact of disease, while FEV1 and FVC measure lung function. Consistency across different types of measures could provide a broader picture, but one outcome cannot be substituted for another. The primary endpoint remains the one-year SGRQ comparison, and secondary summaries do not resolve the uncertainty in that primary estimate.

Multiple outcomes create a multiplicity concern: when many comparisons are considered, the chance of at least one seemingly notable result can increase. Unadjusted secondary results do not account for that issue. They also require caution because the registry record does not state how these outcomes were selected for analysis, whether any were prespecified as confirmatory, or whether adjustment for multiple testing was planned. These results are best read as descriptive context, not as independent confirmation of the primary finding.

The registry lists repeated FEV1 and FVC outcome titles in its outcome information and reports five secondary outcomes, while no secondary analyses are listed. The record does not explain the relationship between every listed outcome entry and the posted summaries. This reporting limitation further supports a cautious, outcome-by-outcome interpretation rather than treating the secondary results as a unified test of the study's aims.

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

• Change in Forced Expiratory Volume in One Second (FEV1)
• Change in Forced Vital Capacity (FVC)
• Change in Forced Vital Capacity (FVC)
• Change in St. George Respiratory Questionnaire (SGRQ) Scores
• Change in Forced Expiratory Volume in One Second (FEV1)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it is a score on a scale, summarized by a mean and standard deviation. A mean describes the arithmetic average in a group. A standard deviation describes how dispersed individual scores are around that average. It is not the uncertainty in the group mean itself; uncertainty in a mean difference is represented by a confidence interval.

What does the mean difference describe?

The posted comparison is the mean in the low-dose theophylline group minus the mean in the placebo group. The estimate is -6.04. A negative estimate means that the reported average score was lower in the low-dose theophylline group. Because higher SGRQ scores correspond to more limitations, the direction is consistent with fewer reported limitations on average in that group. This arithmetic direction does not establish that the treatment caused the difference or that the size is important to patients.

The comparison is unadjusted: it uses the posted group summaries without accounting for other variables. The recalculated comparison is a simple unadjusted re-calculation from the posted summary statistics. The registry record does not report a sponsor analysis or a statistical model for this endpoint. It therefore does not establish whether any sponsor analysis used adjustment, a different method, or a different analysis population.

What does the confidence interval add?

A confidence interval describes a range of values compatible with the observed data under the assumptions of the interval's calculation. It expresses uncertainty about the estimated mean difference, rather than a range containing a specified proportion of individual participants' scores. The recalculated unadjusted interval is -14.41 to 2.333. Since it includes 0, the data do not sharply distinguish a negative mean difference from no difference or a positive mean difference under this calculation.

Confidence intervals depend on assumptions about the data and the method used to calculate them. The interval posted for this comparison is a simple unadjusted calculation. The registry record does not report whether the trial's own analysis used a different interval method or accounted for baseline values, missing outcomes, or other covariates.

How should the p-value be read?

The recalculated unadjusted p-value is 0.157. In general, a p-value measures how unusual results at least as inconsistent with a specified null model would be if that model and the calculation assumptions were correct. It is not the probability that the null hypothesis is true, and it does not measure the probability that a result will replicate. A p-value is also not a measure of clinical importance. Here, its interpretation is limited because the registry record does not report the trial's complete analysis plan or a sponsor-reported analysis.

The confidence interval and p-value address related questions about statistical uncertainty, but neither substitutes for considering the size of the estimate, the measurement scale, the outcome's importance, and the quality and completeness of the data. The SGRQ scale indicates the direction of better or worse scores, but the registry record does not report a threshold for a clinically important difference.

Why does variability matter?

Participants' scores vary within each group. When individual outcomes are variable relative to the mean difference, the estimated comparison can be imprecise. The standard deviations in the registry describe this outcome variability. They are not standard errors or confidence limits. A standard error, in general, describes the estimated variability of a statistic across repeated samples under a statistical model; the registry lists standard errors for the group means in its derived comparison information.

Over-dispersion is a general concern when data vary more than a model assumes. In such settings, standard errors can be too small if a model does not account for the extra variability, making intervals too narrow and evidence appear more precise than it is. The primary outcome is a continuous score, and the registry does not report that an over-dispersion adjustment was used or needed. It would be inappropriate to infer a model problem from the summary statistics alone.

What cannot be established from the summaries?

Group means and standard deviations do not reveal the shapes of the score distributions, whether there were outliers, the pattern of individual change, or how missing values were handled. The registry record does not report the primary outcome's analysis population, a detailed missing-data strategy, covariate adjustment, or the trial's prespecified statistical methods. These are important for judging whether a simple summary-based comparison matches the planned and reported trial analysis.

Random assignment is intended to support a fair comparison by balancing prognostic factors on average, but the record's brief design description does not supply the detailed methods needed to evaluate implementation. The recalculated estimate is therefore a descriptive, unadjusted comparison of posted results. It should be distinguished from a complete trial analysis and interpreted alongside the registry's reporting limitations.

11. Confidence Intervals and Precision

The primary mean difference is -6.04 SGRQ points, with a recalculated unadjusted confidence interval from -14.41 to 2.333. The interval spans 0, so it includes values corresponding to a lower average score in the low-dose theophylline group, no average difference, and a higher average score in that group. The point estimate alone gives a single value, while the interval makes the uncertainty around it visible.

The interval is broad relative to the point estimate. This means the posted data do not pin down the size of the between-group difference precisely. The lower and upper limits represent uncertainty about the mean difference under the calculation's assumptions, not the range of scores experienced by individual participants. The group standard deviations, 21.0 and 16.87, describe individual score variation and should not be confused with the confidence interval.

The p-value, 0.157, is consistent with the interval's inclusion of 0 in this unadjusted comparison. Neither statistic proves equivalence or establishes that there is no difference. A wide interval can include estimates that might be interpreted differently in practical terms, and the registry does not report a threshold for a clinically important SGRQ difference. Statistical uncertainty and clinical interpretation are separate questions.

The calculations are unadjusted recalculations from the posted summary statistics. The registry record does not report a sponsor analysis for this endpoint, the prespecified interval method, or details of how missing outcome data were treated. Those omissions limit how fully the precision of the trial's own analysis can be assessed.

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 figures are planning illustrations based on the observed effect, not the trial's original design assumptions. For these continuous-outcome comparisons, the figures refer to participants per arm, not total events. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to be detected is the stated fraction of the observed effect.

The 80% power column gives the planned number of participants per arm under which a study would have an 80% probability of detecting the specified effect at the stated significance level, if the assumptions hold. The 90% power column uses a higher probability of detecting that effect and therefore generally requires more participants per arm. These are planning quantities, not a guarantee that a future study will find a statistically significant result.

Rows describing 100%, 75%, and 50% of the observed effect ask what the planning requirements would be if the target effect were the full observed estimate or a smaller fraction of it. Smaller effects need more participants to distinguish them from random variation at the same power and significance level. The curve communicates the same general relationship between a target effect and the required sample size; it is a planning aid rather than evidence about treatment efficacy.

The observed effect is estimated with uncertainty, and using it as a planning reference can make a future target overly optimistic or otherwise unrepresentative. The registry record does not report the trial's original sample-size justification or design assumptions. These figures are not observed power; they are illustrations under the stated planning assumptions.

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 = -6.040; pooled standard deviation σ = 18.995.
2. n = 2 × (1.96 + 0.842)² × 18.995² / -6.040² = 155.2, rounded up to 156 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 <- -6.04                      # observed difference in means
sigma <- 18.9945592749946                     # 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(3984188)
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 = 156 (80% power), 208 (90% power)
 75% of observed effect: n per arm = 276 (80% power), 370 (90% power)
 50% of observed effect: n per arm = 621 (80% power), 832 (90% power)
power.t.test: 156.2 
Simulated power at n = 156 per arm: 0.805 (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. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary endpoint and several secondary outcomes, including measures of lung function and SGRQ at a different follow-up time. Testing multiple outcomes can increase the chance of a result appearing notable by chance. A prespecified multiplicity strategy can control or describe that risk, but the registry record does not report whether an adjustment, hierarchy, or other multiplicity plan was used. The unadjusted secondary comparisons therefore carry less evidential weight than a clearly prespecified primary analysis.

The record lists no reported analyses for the secondary outcomes. It also does not provide a full statistical analysis plan, so it is not possible to determine which comparisons were planned as confirmatory, how many analyses were intended, or whether any analyses were added after results were examined. The primary comparison described in the statistical interpretation is a simple unadjusted recalculation, not a substitute for an analysis plan.

Missing outcome data can affect both the precision and validity of a comparison, especially if the probability of missingness is related to health status or treatment assignment. The registry reports outcome-specific group counts, but does not explain why those counts differ across outcomes, whether participants were excluded, or how missing values were handled. It does not report imputation methods, sensitivity analyses, or a detailed flow of participants through follow-up.

The analysis populations are also not reported in the registry record. It is therefore unclear from the posted results whether the primary comparison includes all randomized participants, only participants with observed outcomes, or another defined population. The record does not describe adherence handling, protocol deviations, or whether the analysis followed an intention-to-treat principle. These gaps prevent a complete assessment of attrition, analysis choices, and the robustness of the reported comparison.

15. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hospitalization for respiratory failure (6.0%), renal failure (2.0%), hospitalization for anemia (2.0%), hospitalization for stroke (2.0%), hospitalization for failure to thrive (2.0%).

The registry lists serious adverse events among 50 participants at risk in the low-dose theophylline group, with 5 affected, and among 49 at risk in the placebo group, with 3 affected. It also lists other adverse events among 50 at risk in the low-dose theophylline group, with 26 affected, and among 49 at risk in the placebo group, with 19 affected. Deaths are listed as 2 in the low-dose theophylline group and 4 in the placebo group.

These counts describe the registry's safety entries; they do not establish that an event was caused by the assigned treatment. The record does not provide enough detail in these summaries to determine event timing, severity beyond the serious-event classification, recurrent events, or the relationship of each event to treatment. The at-risk counts are safety-specific and should not be assumed to be the analysis denominators for the efficacy outcomes.

The most frequently listed serious-event term is hospitalization for respiratory failure, reported as 6.0%. Renal failure, hospitalization for anemia, hospitalization for stroke, and hospitalization for failure to thrive are each reported as 2.0%. These registry entries should be interpreted descriptively. The listed events and percentages do not by themselves support a comparative safety conclusion.

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

The posted primary result describes a mean SGRQ score that was lower in the low-dose theophylline group than in the placebo group at one year. Because higher SGRQ scores indicate more limitations, the direction of the estimate corresponds to fewer limitations on average in the low-dose theophylline group. The confidence interval includes 0 and extends across effects in either direction, so the summary does not precisely establish the size or direction of the underlying mean difference.

This is not evidence that every participant experienced the group-average result. A mean can conceal varied individual experiences, and the posted summaries do not show the distribution of changes or the proportion of participants whose scores improved. The registry record also does not report a threshold for a clinically important SGRQ difference, making it difficult to assess the practical importance of the point estimate from the score alone.

The result is limited to the primary outcome and follow-up reported. It does not resolve the study's other stated aims concerning serum biomarkers, whether administration attenuates the effect of household air pollution on lung function, or cost-effectiveness. The record does not post secondary analyses that would allow those questions to be evaluated statistically.

Randomization and masking are important design features, but a complete interpretation also depends on implementation, outcome completeness, analysis choices, and the handling of missing data. Details on these matters are not reported in the registry record. The statistical summaries therefore describe the posted comparison, not a definitive conclusion about clinical benefit, absence of benefit, or safety.

Results from adults with biomass-associated COPD in Uganda should not automatically be generalized to other populations or disease contexts. The registry's own summary distinguishes biomass-related COPD from tobacco-mediated COPD, and the reported trial question is specific to the former setting. The record does not supply evidence to establish how these results apply outside the studied population.

17. Why This Trial Matters Statistically

This trial is statistically informative because it focuses on a population and exposure context that the registry describes as distinct from tobacco-mediated COPD. The results therefore raise questions about how a therapy comparison should be interpreted when the target disease context is specific and when clinical outcomes may not be interchangeable across populations.

The primary endpoint is a patient-reported measure, while the listed secondary outcomes include measures of lung function. Those outcomes capture different dimensions of disease. Comparing them can be useful, but it also makes clear why a primary endpoint should be identified in advance and why secondary comparisons need careful interpretation when several outcomes are assessed.

The primary point estimate is in the direction of a lower SGRQ score in the low-dose theophylline group, but its unadjusted confidence interval includes 0. This illustrates the difference between the direction of an estimate and the certainty of evidence about that estimate. Reporting a mean difference with an interval helps readers assess both, rather than relying only on a single point estimate or p-value.

The registry record also highlights how much interpretation depends on reporting quality. Without a detailed analysis plan, missing-data methods, analysis populations, and reported secondary analyses, readers cannot fully assess whether the posted summaries correspond to the intended analyses. Planning illustrations based on an observed effect can help explain how study size relates to a target effect, but they cannot replace the original design justification.

For biostatistical interpretation, this is a reminder to separate descriptive group summaries, unadjusted calculations, and prespecified trial analyses. Each supports a different level of inference. The distinction matters especially when the primary result is imprecise and the registry does not report the analyses needed to resolve related clinical questions.

18. 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 affect interpretation of the posted results. The registry reports an enrollment of 100, while the primary endpoint summaries include 39 participants in the low-dose theophylline group and 41 in the placebo group. The record does not explain the difference between enrollment and these outcome counts, whether participants lacked follow-up scores, or how the available outcome data were handled. Outcome-specific counts also vary for secondary measures.

The registry does not report a detailed statistical analysis plan, the original sample-size justification, the analysis population, or the model used for the trial's own primary analysis. The recalculated comparison uses posted summary statistics and is unadjusted. The record does not state whether an analysis accounting for baseline score or other variables was conducted, or whether the posted summary matches the prespecified analysis.

The clinical interpretation of the SGRQ estimate is also limited because no threshold for a clinically important difference is reported. The registry provides the scale's direction and range, but not a study-specific interpretation threshold. Group means and standard deviations do not show how individual participants' scores changed or whether outcomes were skewed.

The record lists secondary outcomes but no reported secondary analyses. It does not report a plan for multiplicity, so those outcomes cannot be considered strong independent confirmation of the primary result. The safety summaries are also descriptive and do not provide enough detail about timing or treatment relatedness to support causal comparisons.

Finally, the results concern adults with biomass-associated COPD in Uganda. The registry does not establish whether the findings apply to other populations, settings, or forms of COPD. These limitations do not negate the posted data, but they constrain the conclusions that can be drawn from them.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Effectiveness of Low-Dose Theophylline for the Management of Biomass-Associated COPD — NCT03984188.
• Registry record last updated 2024-11-15; status last verified 2024-10.
• Results first posted 2024-10-29.
• 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.

22. Record Summary

The registry record describes a completed phase 3, randomized, quadruple-masked, parallel-group trial sponsored by the University of Miami. It compares low-dose theophylline plus standard care with placebo plus standard care among adults with biomass-associated COPD in Uganda. The primary endpoint is change in SGRQ score from baseline to one year.

The reported one-year means are 39.02 in the low-dose theophylline group and 45.06 in the placebo group. The unadjusted recalculated mean difference is -6.04, with a 95% confidence interval from -14.41 to 2.333 and p = 0.157. The interval includes 0, and the result is imprecise. The registry lists secondary outcomes but no reported secondary analyses.

The record does not report the original sample-size justification, full statistical analysis plan, missing-data methods, or analysis populations. The posted summaries support a cautious description of the observed comparison, not a definitive conclusion about clinical benefit or safety.