This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Indomethacin Germinal Matrix Hemorrhage/Intraventricular Hemorrhage (GMH/IVH) Prevention Trial (NCT00033917), a randomized phase 3 study. The primary outcome is IVH at 5 Postnatal Days.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00033917 |
| Phase | Phase 3 |
| Condition | Intraventricular Hemorrhage (IVH), Bleeding in the Brain, Prematurity |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 630 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Yale University |
| Results posted | Yes |
2. Clinical Question
Population
The trial concerned very low birth weight preterm infants. The primary-outcome description says all subjects had negative cranial ultrasounds, with no evidence of IVH, at 6 - 12 postnatal hours. This identifies the group described for assessing IVH during the following postnatal days; additional eligibility criteria and the precise definition of very low birth weight are not reported in the registry record. The registry lists 630 participants enrolled overall.
Intervention
The intervention was indomethacin, listed as a drug. The registry describes the study as randomized, double-masked, and parallel-group, but does not specify the dose, route, schedule, or duration of treatment. Those details are not reported in the registry record.
Comparator
The comparator was placebo, also listed as a drug. The registry names the two arms Indomethacin and Placebo. It does not describe the placebo's composition or provide further details about how treatment assignment was concealed or how masking was maintained.
Primary question
The primary question was whether indomethacin prevents IVH in this population. The listed primary outcome is IVH at 5 postnatal days. Cranial ultrasounds were performed daily for the first 5 postnatal days, and the main outcome measure was IVH at 5 days of age. The registry reports 25.0 for the indomethacin arm, with 209.0 participants, and 40.0 for the placebo arm, with 222.0 participants. These are reported counts; the registry does not provide a comparative estimate, confidence interval, or significance test for this endpoint.
3. Trial Design
The registry describes a Phase 3, randomized, double-masked, parallel-group trial comparing indomethacin with placebo. Its title is “Indomethacin Germinal Matrix Hemorrhage/Intraventricular Hemorrhage (GMH/IVH) Prevention Trial,” and Yale University is listed as sponsor. The brief summary describes it as a multicenter trial intended to determine whether indomethacin prevents bleeding in the brain of very low birth weight preterm infants.
The registry lists 630 participants enrolled. The primary endpoint results are reported for an indomethacin arm of 209.0 and a placebo arm of 222.0. The record does not explain how these endpoint denominators relate to the total enrollment, so they should not be treated as a complete accounting of all enrolled participants. Reasons for any difference, including exclusions or unavailable outcome measurements, are not reported in the registry record.
The trial start is recorded as 1989-09, the primary completion as 2012-03, and the status as completed. The registry does not give further details about the timing or duration of recruitment, follow-up, or treatment. It also does not identify which people were masked, describe the randomization sequence or allocation concealment, or list the participating centers.
Two outcome measures are listed, including the primary IVH outcome and a secondary Language Outcome. The registry does not include posted analyses for either outcome. A detailed protocol, statistical analysis plan, sample-size justification, interim-analysis plan, and participant flow are not reported in the registry record. The design labels establish the broad structure of the trial, but do not supply those operational or analytical details.
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: Cranial ultrasounds were performed on all study participants between 6 - 12 hours of age for group assignment. Subjects with major congenital cerebral malformations were excluded.
Overall Study
| Stage | IVH Negative Indomethacin | IVH Negative Placebo |
|---|---|---|
| STARTED | 209 | 222 |
| COMPLETED | 209 | 222 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: All subjects had negative cranial ultrasounds with no evidence for IVH at 6 - 12 postnatal hours
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.
| Characteristic | Unit | Indomethacin | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 209 | 222 | 431 | |
| Age Continuous | hours | 7.8 (SD 2.3) | 7.9 (SD 2.4) | 7.8 (SD 2.3) |
| Sex: Female, Male: Female | Participants | 93 | 103 | 196 |
| Sex: Female, Male: Male | Participants | 116 | 119 | 235 |
| Region of Enrollment: United States | participants | 209 | 222 | 431 |
6. Primary Endpoint
The registry lists the primary outcome as IVH at 5 Postnatal Days, measured over at 5 days.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | IVH |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is titled “IVH at 5 Postnatal Days.” Its unit is IVH, and its outcome type is recorded as a number. The description states that cranial ultrasounds were performed daily for the first 5 postnatal days and that the main outcome measure was intraventricular hemorrhage at 5 days of age. It also states that all subjects had negative cranial ultrasounds, with no evidence of IVH, at 6 - 12 postnatal hours.
This endpoint focuses on whether IVH is detected during the early postnatal period among the population described as having no evidence of IVH on the initial ultrasound. Serial cranial imaging provides a way to identify the outcome during the stated observation period. The registry's brief summary frames the trial around prevention of bleeding in the brain in very low birth weight preterm infants; the endpoint therefore records the occurrence of IVH in that context.
The registry reports 25.0 for indomethacin and 40.0 for placebo, alongside arm sizes of 209.0 and 222.0. It does not specify in the outcome entry whether these values count participants with IVH, individual hemorrhages, or another event-counting unit beyond the label and unit IVH. The timing of outcome ascertainment is stated, but detailed grading criteria, adjudication procedures, and handling of repeated or uncertain ultrasound findings are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary-outcome values are 25.0 in the indomethacin arm and 40.0 in the placebo arm. The corresponding reported arm sizes are 209.0 and 222.0. These are counts, not a reported treatment-effect estimate. The registry record does not present a risk difference, relative measure, confidence interval, or statistical test for the primary comparison. Because the endpoint is recorded as a number and the registry does not fully define the unit counted, the counts should be interpreted according to the registry's description rather than converted into a different measure.
The values are not identical across arms, but the posted figures alone do not establish how precisely the arms differ or whether the difference is compatible with chance variation. A comparative analysis would need to account for the outcome definition, the allocation, the analysis population, and the variability of the observed counts. Those analytical details are not included in the posted results. No inferential conclusion should be drawn from the counts without that information.
The registry describes randomization and double masking, which are important features for limiting some forms of bias in a trial. However, it does not report the randomization method, concealment procedures, which groups of people were masked, or whether masking was maintained. These missing details limit the ability to assess how the trial was conducted from the registry record alone. The record also does not provide a participant flow diagram or explain how the primary-outcome denominators relate to the enrollment of 630.
The endpoint description specifies daily cranial ultrasounds during the first 5 postnatal days and a primary outcome at 5 days of age. It also identifies a negative cranial ultrasound at 6 - 12 postnatal hours for all subjects. The posted entry does not give a longer-term IVH outcome, severity breakdown, or a comparative result for the secondary Language Outcome. A single short-term count cannot answer questions beyond the outcome and follow-up period that are documented.
There are no posted analyses in the registry record. This means the registry entry does not offer a sponsor-reported treatment-effect estimate or its uncertainty for the primary endpoint. It does not establish that the trial had no analysis; it means the results record lacks an analysis to interpret. Any sample-size figures associated with the posted results are planning illustrations based on the observed effect and stated assumptions, not observed power and not evidence of the trial's original design rationale. The design assumptions underlying the original trial are not reported in the registry record.
9. Statistical Methods Explained
Interpreting a trial result requires distinguishing the endpoint itself from the statistical comparison. The registry describes a randomized, double-masked, parallel-group study, with IVH at 5 postnatal days as the primary endpoint. It reports a count for each arm, but does not post an analysis that estimates the contrast between the arms. The reported values therefore describe the outcome record, while leaving the size and precision of any treatment contrast unquantified.
What does the count represent?
A count outcome records how many events or observations meet an outcome definition. Here, the registry labels the outcome as IVH and reports 25.0 for indomethacin and 40.0 for placebo. It does not clarify whether each count represents participants who experienced IVH, individual IVH events, or another counting convention. That distinction matters: a count of affected participants has a different interpretation from a count that can include multiple events for one participant. The record's label and description should therefore be retained without assuming an unreported counting rule.
The arm sizes are 209.0 and 222.0, but denominators alone do not resolve the event definition or tell how missing outcome observations were handled. The total enrollment is 630; the record does not reconcile that total with the arm sizes shown for this endpoint. It is not appropriate to infer the reasons for that difference or to assume that every enrolled participant contributed to the reported endpoint counts.
Why is a comparative estimate useful?
A treatment comparison expresses how the observed outcome differs between randomized groups using a defined statistical measure. For a count outcome, the appropriate measure depends on what is counted, how participants contribute to the count, the follow-up structure, and assumptions about the distribution of outcomes. Possible approaches may use an event-rate contrast or a model for counts, but the registry does not identify a method used for this endpoint. No new comparison can be reconstructed from the posted information without choosing assumptions that are not in the record.
A confidence interval is a statistical range that describes the uncertainty around an estimated effect under the assumptions of the analysis. It can help readers distinguish a relatively precise estimate from one that is compatible with a broad range of effects. The registry does not report a confidence interval for the primary comparison. Nor does it report a p-value or a sponsor's inferential result. The arm counts alone do not provide those measures.
Why can count variability matter?
In general, count outcomes can vary more than a simple model assumes. Over-dispersion means the observed variability is greater than the variability assumed by a chosen count model. If over-dispersion is present and ignored, uncertainty estimates may be too narrow, making the result appear more precise than the data support. This is a general statistical consideration, not a finding about this trial: the registry does not report a dispersion estimate, a count model, or an assessment of over-dispersion.
Other features can also affect the analysis. Counts may be clustered by center, repeated within a participant, or influenced by differing observation time, but the registry does not state whether any of these features applied or how they were handled. The brief summary calls the study multicenter; the number and identity of centers, and any center adjustment, are not reported in the registry record. The outcome is described at 5 days, but no detail is given about whether observation time varied among participants.
What do randomization and masking contribute?
In general, randomization assigns participants to groups using a chance-based process. When appropriately implemented, it aims to make treatment groups comparable with respect to both measured and unmeasured characteristics at the start of a trial. Masking aims to limit the influence of treatment knowledge on care, outcome assessment, or reporting. These are general principles, not a verification of how they were implemented in this study. The registry records the trial as randomized and double-masked but does not specify the sequence-generation or concealment method, who was masked, or the success of masking.
The parallel-group label means the registry describes separate indomethacin and placebo arms. It does not by itself establish whether the analysis followed assignment regardless of treatment received, excluded participants after randomization, or used another population definition. The primary analysis population and the handling of treatment changes are not reported in the registry record.
How should planning illustrations be understood?
General sample-size calculations use assumptions about the effect to detect, variability, significance level, allocation, and analysis method. The planning illustrations associated with the posted results are described as using a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect stated as a fraction of the observed effect. For non-time-to-event outcomes, such figures are participants per arm for the stated power. These are planning illustrations based on the observed effect, not the trial's own design calculation and not observed power. The original sample-size justification is not reported in the registry record.
Observed power is not a substitute for an estimate and confidence interval: it is not a measure of how much uncertainty remains around the observed effect. A planning illustration asks what sample size might be needed under its stated assumptions; it does not show that the trial achieved that power or establish why the investigators selected the enrolled number. Because the registry does not post a comparative analysis or the original design justification, those questions remain unanswered for this trial.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists two outcome measures: the primary IVH outcome and a secondary Language Outcome. It does not report a multiplicity strategy, such as whether the primary outcome was the sole confirmatory test or whether adjustment was planned for multiple outcomes. Without a prespecified hierarchy or adjustment method, the registry record does not establish how the chance of false-positive findings across outcomes was addressed. No posted analyses are available for either outcome, so there are no reported outcome-specific estimates or tests to assess.
Missing-data handling is not reported in the registry record. The primary endpoint lists 209.0 participants in the indomethacin arm and 222.0 in the placebo arm, while total enrollment is 630. The registry does not explain how those numbers relate to each other, whether any endpoint observations were unavailable, or whether participants were excluded from the endpoint analysis. It does not describe imputation, censoring, sensitivity analyses, or procedures for handling incomplete or unreadable ultrasound assessments.
The analysis population is also not reported in the registry record. In particular, the entry does not say whether the primary comparison used all randomized participants according to assigned group, only participants who received treatment, or another population. These are distinct analysis choices and can affect interpretation. Randomized allocation is recorded, but the presence of randomization alone does not identify the population used for the reported counts.
The record also does not state whether interim analyses were planned or conducted, or whether any stopping rules were specified. These details should not be inferred from the trial's Phase 3 designation, enrollment, or completed status.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| IVH Negative Indomethacin | 0 | 208 | 0.0% |
| IVH Negative Placebo | 0 | 222 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| IVH Negative Indomethacin | 19 of 209 |
| IVH Negative Placebo | 12 of 222 |
Most frequent non-serious adverse event terms
| Event term | Organ system | IVH Negative Indomethacin | IVH Negative Placebo |
|---|---|---|---|
| decreased urine output | Renal and urinary disorders | 19 of 209 | 10 of 222 |
| excessive bleeding | Blood and lymphatic system disorders | 9 of 209 | 10 of 222 |
| ischemic changes by ECHO | Nervous system disorders | 6 of 209 | 12 of 222 |
| creatinine > 1.8 mg/dL | Renal and urinary disorders | 5 of 209 | 5 of 222 |
| platelets < 50,000 | Blood and lymphatic system disorders | 2 of 209 | 4 of 222 |
| necrotizing enterocolitis | Gastrointestinal disorders | 2 of 209 | 0 of 222 |
The registry reports adverse-event figures for groups labeled “IVH Negative Indomethacin” and “IVH Negative Placebo.” For serious adverse events, the number affected is 0 in each group; the corresponding numbers at risk are 208 and 222. For other adverse events, the number affected is 19 in the indomethacin group and 12 in the placebo group; the numbers at risk are 209 and 222. These are counts, and no rates or comparative safety estimates are reported.
The registry does not list serious adverse-event terms, and the event details, severity criteria, observation window, and method of collection are not reported in the registry record. The “other adverse events” category is not defined in the entry. The group labels indicate IVH-negative groups, but further information about how participants entered those safety groups is not given. Deaths are not reported in the registry record; a missing deaths value should not be read as zero.
These figures should be read as the recorded affected counts and their stated denominators, not as a complete account of safety or as proof of a difference between arms. The registry does not provide confidence intervals, tests, event-level descriptions, or an explanation of missing safety information. The figures alone cannot establish the comparative frequency, seriousness, timing, or cause of adverse events.
12. What the Result Does, and Does Not, Mean
The posted primary outcome records 25.0 IVH for the indomethacin arm and 40.0 for the placebo arm, with arm sizes of 209.0 and 222.0. This is a descriptive comparison of the registry's reported counts. It does not, on its own, establish the magnitude or precision of a treatment effect. The registry provides no comparative estimate, confidence interval, or statistical test for the primary outcome.
The result is specific to IVH as recorded at 5 postnatal days in the population described as having negative cranial ultrasounds at 6 - 12 postnatal hours. It does not report a severity classification, longer-term IVH status, or other clinical outcomes beyond the listed secondary Language Outcome. Results for that secondary outcome are not posted. The registry therefore does not support conclusions about outcomes that were not reported or about follow-up beyond the stated primary endpoint.
The record characterizes the trial as randomized, double-masked, and parallel-group, but provides limited detail about those procedures. It does not describe the randomization method, allocation concealment, or who was masked. The primary analysis population, missing-data methods, and statistical model are also not reported. These gaps make it difficult to assess the analysis underlying the counts or the uncertainty around any comparison.
Numerical sample-size illustrations are planning exercises based on an observed effect and stated assumptions. They are not observed power, do not replace a confidence interval, and do not explain the trial's original design. The original design rationale is not reported in the registry record.
Accordingly, the posted results document outcome counts and selected design details, but they do not provide the inferential analysis needed to characterize the comparative effect precisely. The counts should not be treated as a complete statement of what the trial established.
13. Why This Trial Matters Statistically
This trial is statistically notable in the registry because it combines a randomized, double-masked, parallel-group design with a clearly timed primary outcome: IVH at 5 postnatal days. The record describes daily cranial ultrasounds during the first 5 postnatal days and an initial negative ultrasound at 6 - 12 postnatal hours. These details help situate the endpoint as an early postnatal outcome rather than an outcome with an unspecified assessment time.
At the same time, the posted primary results are counts without a corresponding comparative analysis. The registry reports 25.0 in the indomethacin arm and 40.0 in the placebo arm, but no effect estimate or uncertainty interval. This distinction is important in biostatistics: descriptive results identify what was recorded, while inferential statistics quantify the contrast and its precision under an explicit analysis method. The latter is not available in the registry entry.
The record also illustrates why denominator and analysis-population details matter. The endpoint arm sizes are 209.0 and 222.0, while enrollment is 630. Without participant flow or an explanation of the analysis population, readers cannot determine how the endpoint counts relate to all enrolled participants. Missing-data procedures and the handling of exclusions are not reported.
Finally, the trial has a listed secondary Language Outcome, but the registry does not post its analysis or explain how multiple outcomes were handled. Together, these features make the record useful for understanding the study's broad design and endpoint, while demonstrating the limits of interpreting registry counts without a posted analysis plan, outcome definition details, and measures of uncertainty.
14. 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 in the registry record constrain interpretation. The primary outcome is described as IVH at 5 days, and the values are reported as numbers, but the entry does not fully clarify whether the counts represent affected participants or events. It gives no grading system, adjudication approach, or procedure for resolving uncertain ultrasound findings. These details are important for understanding what the reported outcome counts capture.
The endpoint arm sizes, 209.0 and 222.0, do not account for the total enrollment of 630 in the information shown. The registry does not provide participant flow, explain exclusions, or state how many participants had an available primary outcome. It also does not identify the primary analysis population or describe missing-data methods. The reason for any difference between enrollment and endpoint denominators is not reported in the registry record.
Although the study is labeled randomized and double-masked, the registry does not describe sequence generation, allocation concealment, which people were masked, or whether masking was maintained. Treatment dose and schedule are not listed. The multicenter description is present in the brief summary, but the number of centers and any center-level analysis are not reported.
The registry does not post an inferential analysis for the primary endpoint or the secondary Language Outcome. It does not report a confidence interval, a statistical test, a multiplicity strategy, or a model for the count outcome. The safety entry lacks event terms, follow-up windows, and definitions for the broad adverse-event categories. These limitations concern the registry record; they do not establish that the trial itself lacked these procedures or analyses.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Indomethacin Germinal Matrix Hemorrhage/Intraventricular Hemorrhage (GMH/IVH) Prevention Trial — NCT00033917.
- Registry record last updated 2013-03-28; status last verified 2013-02.
- Results first posted 2013-03-28.
- 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.
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18. Record Summary
The registry record identifies NCT00033917 as the Indomethacin Germinal Matrix Hemorrhage/Intraventricular Hemorrhage (GMH/IVH) Prevention Trial, sponsored by Yale University. It is listed as a completed Phase 3 randomized, double-masked, parallel-group trial with 630 participants enrolled. The trial compared indomethacin with placebo in very low birth weight preterm infants.
The primary outcome was IVH at 5 postnatal days, after daily cranial ultrasounds during the first 5 postnatal days. The registry reports counts of 25.0 for indomethacin and 40.0 for placebo, with respective arm sizes of 209.0 and 222.0. A secondary Language Outcome is listed, but no analyses are posted. The registry does not report a comparative statistical estimate or its uncertainty for the primary endpoint, nor does it explain the endpoint denominators, analysis population, or missing-data handling.