Study of Oral Ibrutinib Capsules to Assess Respiratory Failure in Adult Participants With Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and Pulmonary Injury: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Oral Ibrutinib Capsules to Assess Respiratory Failure in Adult Participants With Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and Pulmonary Injury (NCT04375397), a randomized phase 2 study. The primary outcome is Percentage of Participants Alive and Without Respiratory Failure Through Day 28.

2. Clinical Question

The primary objective recorded for the study was to evaluate whether ibrutinib was safe and could reduce respiratory failure in participants with COVID-19 infection. The registry lists additional outcomes covering the WHO-8 Ordinal Scale at Study Day 14, time on supplemental oxygen, mortality at several study days, respiratory failure or death at several study days, mechanical ventilation, and hospital discharge and duration. These outcomes provide other ways to describe clinical course, but their presence does not establish that an effect was observed.

3. Trial Design

This completed phase 2 study, NCT04375397, was a randomized, quadruple-masked, parallel-group comparison of ibrutinib plus standard care with placebo plus standard care. The registry lists an enrollment of 46. The study started on 2020-06-06, and primary completion was recorded as 2021-05-10. AbbVie is listed as the sponsor.

The active-treatment group received 420 mg ibrutinib once daily as three capsules, each containing 140 mg, with approximately 240 mL of water, for up to 28 days, alongside supportive care. The placebo group received three placebo capsules once daily with approximately 240 mL of water, also for up to 28 days and alongside supportive care. The record identifies the primary endpoint population as the Full Analysis Set: all randomized participants who received at least 1 dose of study drug. The arm counts for the primary endpoint were 22 for ibrutinib plus SOC and 24 for placebo plus SOC.

The primary outcome was assessed through Day 28. The registry also lists secondary outcomes, including change in the WHO-8 Ordinal Scale from baseline at Study Day 14; reduction in days spent on supplemental oxygen; all-cause mortality; respiratory failure or death; mechanical ventilation-free survival; days on mechanical ventilation; hospitalization duration; and time to discharge. The record lists 12 outcome measures, 29 analyses, and 11 posted secondary outcomes. The details of how those outcomes were analyzed are not reported in the registry record.

Randomization and masking describe the planned design, but the registry record does not report the method used to generate or conceal the allocation sequence, or the identities of the masked parties. It also does not report the study’s original sample-size assumptions or the rationale used to select the enrollment target. Those details should not be inferred from the planning illustrations based on the observed result.

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: Full Analysis Set (FAS): all randomized participants who received at least 1 dose of study drug

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set (FAS): all randomized participants who received at least 1 dose of study drug

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: Full Analysis Set (FAS): all randomized participants who received at least 1 dose of study drug

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Alive and Without Respiratory Failure Through Day 28, measured over Through Day 28.

The primary endpoint is the percentage of participants who were alive and without respiratory failure through Day 28. It combines survival and respiratory status into one binary outcome: each participant either met the stated endpoint or did not. The reported arm estimates were 86.4% for ibrutinib plus SOC and 79.2% for placebo plus SOC.

Respiratory failure was defined using both a clinical diagnosis and initiation of specified support: endotracheal intubation and mechanical ventilation; extracorporeal membrane oxygenation; high-flow nasal cannula oxygen delivery; or non-invasive positive pressure ventilation. The definition also included a clinical diagnosis of respiratory failure without those measures when the clinical decision was driven solely by resource limitation. For high-flow nasal cannula, the definition specifies heated, humidified oxygen, a delivered-oxygen fraction of at least 0.5, and flow rates of at least 30 L/min.

A combined endpoint can summarize whether participants remained alive without the specified respiratory-failure event over a defined period. It does not, by itself, show which component accounts for the result. The endpoint is used to capture both survival and serious respiratory deterioration in a single measure; separate outcomes are needed to distinguish those components. The registry reports the endpoint and definition, but the endpoint-specific handling of participants with missing assessments is not reported in the registry record.

7. Results Posted in the Registry

• Placebo + SOC: 79.2% (19/24) versus 86.4% (19/22) on control; risk difference -7.2 percentage points (95% CI -28.9 to 14.5), risk ratio 0.92 (0.70–1.19); unadjusted two-proportion z-test p = 0.520.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a binary outcome expressed as a percentage: participants either remained alive without respiratory failure through Day 28 or did not. For such an outcome, the arm-specific percentage describes the observed proportion meeting the endpoint in that arm. In this trial, the posted estimates were 86.4% in the ibrutinib plus SOC arm and 79.2% in the placebo plus SOC arm. Those percentages should be read together with the numbers of participants in each arm and the uncertainty intervals.

What does a risk difference describe?

A risk difference compares the proportions meeting an outcome in two groups by subtracting one group’s proportion from the other’s. It is an absolute contrast on the probability scale, rather than a relative comparison. Its sign depends on which group is subtracted from which. In the unadjusted recalculation, placebo plus SOC is compared with the ibrutinib plus SOC control arm; the reported risk difference is -0.072, with a confidence interval from -0.289 to 0.145. The negative point estimate indicates a lower observed proportion in the placebo arm under that contrast convention, but the interval includes zero and extends in both directions.

What is the difference between the recalculation and the posted analysis?

The unadjusted recalculation uses the posted arm counts and is a simple comparison of the observed proportions. The registry’s own reported analysis uses the Miettinen-Nurminen method and labels its result an adjusted risk difference. It reports 5.8%, with an 80% confidence interval from -9.2% to 20.4% and a 95% confidence interval from -18.1% to 28.7%; the reported p-value is =0.599. An adjusted analysis may use a different procedure or estimand from a simple unadjusted contrast. The exact covariates or other adjustment details are not reported in the registry record, so the adjustment should not be reconstructed or guessed. These analysis results are not interchangeable, even though both address a difference in proportions.

How should a confidence interval be understood?

A confidence interval expresses uncertainty around an estimate under the assumptions of the statistical method. In general, a wider interval indicates less precision, while a narrower interval indicates greater precision. An interval that includes zero for a risk difference does not rule out no difference at the confidence level represented by that interval. Nor does it establish that the groups are equivalent: equivalence requires a prespecified margin and an analysis designed to assess it, and such a margin is not reported in the registry record.

The arm-specific endpoint estimates are accompanied by 80% confidence intervals: 74.4 to 93.2 for ibrutinib plus SOC, and 66.9 to 87.7 for placebo plus SOC. These intervals describe uncertainty around each arm’s percentage separately. They are not a confidence interval for the difference between the arms. For that contrast, the registry’s own adjusted analysis supplies its risk-difference intervals, while the recalculation supplies an unadjusted interval.

What does the p-value add?

In general, a p-value measures how incompatible the observed data are with a specified null hypothesis under the analysis model. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. The sponsor’s reported p-value is =0.599. The unadjusted recalculation reports 0.52. Because these come from different analyses, the p-values should be interpreted in the context of their corresponding methods and contrasts, not combined or treated as competing versions of a single calculation.

Why can the method matter?

Different procedures for comparing proportions may produce different point estimates, intervals, and p-values, particularly when the sample is limited. Adjustment choices can also change the interpretation of a contrast. General statistical practice therefore requires attention to the outcome definition, analysis population, contrast direction, method, and uncertainty interval, rather than relying on a single summary number. The sponsor’s analysis is the registry’s posted trial analysis; the unadjusted calculation is a separate descriptive check based on the posted summary counts. The record does not report enough detail to reproduce the sponsor’s adjustment independently.

The trial is randomized and masked, but those design features do not guarantee precise estimates. Randomization supports a fair comparison in expectation, while the observed counts still vary from trial to trial. Masking can reduce some forms of bias in conduct or outcome assessment, but the registry record does not identify who was masked or describe how masking was maintained. No claim about implementation should go beyond those recorded design labels.

For outcomes involving time to an event, such as time to discharge or mechanical ventilation-free survival, methods can differ from methods for a simple percentage at a fixed time. The registry lists such secondary outcomes, but their detailed analyses and estimates are not reported in the record described for the primary comparison. General concepts about time-to-event analysis should therefore not be used to imply that a particular method was used for those outcomes.

10. Confidence Intervals and Precision

The primary endpoint percentages are estimates from 22 participants assigned to ibrutinib plus SOC and 24 assigned to placebo plus SOC. The 80% confidence interval for the ibrutinib arm is 74.4 to 93.2; for the placebo arm, it is 66.9 to 87.7. These are arm-specific intervals, not intervals for the difference between arms. Their overlap is not a formal test of the treatment contrast; the reported contrast analysis should be used for that purpose.

The sponsor’s adjusted risk difference is 5.8%, with an 80% confidence interval from -9.2% to 20.4% and a 95% confidence interval from -18.1% to 28.7%. Each interval includes zero and permits effects in either direction. The 95% interval is wider than the 80% interval, as expected for an interval with greater confidence. Taken together, the posted estimates leave substantial uncertainty about the size and direction of the difference.

The unadjusted recalculation gives a risk difference of -0.072, with a confidence interval from -0.289 to 0.145. It is also broad and includes zero. The adjusted and unadjusted intervals arise from different analyses and contrast conventions, so they should not be compared as if they estimate exactly the same quantity. Both communicate that the available results are not precise enough to pin down a single direction and magnitude of the treatment-group difference.

Confidence intervals describe sampling uncertainty under the method’s assumptions; they do not account for every possible source of uncertainty, such as limitations in outcome ascertainment or missing data. The registry record does not report enough detail to evaluate those issues fully. A confidence interval also does not tell whether any effect within its range would be clinically important; that judgment depends on criteria not reported in the registry record.

11. 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 planning figures are participants per arm, not total events. They are illustrations based on the observed effect, not the trial’s original design calculation. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; each planning row uses the stated fraction of the observed effect as the effect to detect. The trial’s own sample-size assumptions and justification are not reported in the registry record.

The 80% power column gives the number of participants per arm estimated to be needed for an 80% chance of detecting the stated effect under those planning assumptions, if that effect were the true one and the assumptions held. The 90% power column gives the corresponding per-arm estimate for a 90% chance. These are design-planning quantities: power is a property of a proposed study under specified assumptions, not a measure of what the completed study achieved.

For planning for 100% of the observed effect, the illustration gives 432 participants per arm for 80% power and 577 participants per arm for 90% power. For planning for 75% of the observed effect, the figures are 736 and 984 participants per arm, respectively. For planning for 50% of the observed effect, they are 1,582 and 2,117 participants per arm. Smaller effects require more participants to detect under the same planning framework, because a smaller difference is harder to distinguish from random variation.

These are not observed power. They are hypothetical planning illustrations computed from the observed effect, so the observed estimate itself is an uncertain basis for projecting future sample sizes. They should not be read as the enrollment target chosen for this trial, nor as evidence that the trial was designed using these assumptions.

12. 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, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.864; treatment proportion p₁ = 0.792; average p̄ = 0.828.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.5341 = 1.0469.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5317 = 0.4475.
4. n = (1.0469 + 0.4475)² / (-0.0720)² = 431.1, rounded up to 432 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
p0 <- 0.863636363636364                          # control proportion
p1 <- 0.791666666666667                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^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 (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(4375397)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 432 (80% power), 577 (90% power)
 75% of observed effect: n per arm = 736 (80% power), 984 (90% power)
 50% of observed effect: n per arm = 1,582 (80% power), 2,117 (90% power)
power.prop.test: 431.1 
Simulated power at n = 432 per arm: 0.803 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-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.

13. Analyses Reported by the Sponsor

The sponsor’s own primary analysis is reported as an adjusted risk difference using the Miettinen-Nurminen method. It gives an estimate of 5.8%, an 80% confidence interval from -9.2% to 20.4%, a 95% confidence interval from -18.1% to 28.7%, and a p-value of =0.599. This is the analysis reported in the registry for the trial’s primary comparison.

The separate unadjusted recalculation uses the posted arm counts and gives a risk difference of -0.072 for placebo plus SOC relative to ibrutinib plus SOC, with a confidence interval from -0.289 to 0.145 and an unadjusted p-value of 0.52. Its contrast is expressed in the reverse arm order from the sponsor’s reported comparison, and it is not the sponsor’s adjusted analysis. Differences in method and contrast convention mean that the two estimates should not be read as direct duplicates.

The discrepancy flag is false, so there is no recorded discrepancy requiring the sponsor’s result to take precedence over a conflicting recalculation. The sponsor’s analysis remains the posted trial analysis, while the simple recalculation is a supplementary unadjusted comparison of the displayed counts. Both intervals include zero and are broad; neither provides a precise estimate of the direction and magnitude of the difference. The adjustment details beyond the named method are not reported in the registry record.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple outcomes and analyses: 12 outcome measures, 29 analyses, and 11 posted secondary outcomes. When a study evaluates several outcomes, timepoints, or statistical contrasts, the chance of finding at least one apparently unusual result can increase if no allowance is made for multiple testing. General statistical practice may address this by prespecifying a primary outcome, defining a hierarchy, or adjusting inference across tests. The registry record does not report whether or how multiplicity was handled.

The primary endpoint is identified, and its timeframe is through Day 28. The record also lists secondary outcomes at specified study days and outcomes involving hospitalization, oxygen, and ventilation. It does not report a full testing hierarchy, which analyses were confirmatory or exploratory, whether secondary-outcome p-values were adjusted, or how conclusions were to be drawn across the family of outcomes. Those details should not be inferred from the number of analyses alone.

The primary endpoint population is defined as all randomized participants who received at least 1 dose of study drug. This definition identifies the Full Analysis Set used for the posted primary outcome. The record does not report how many randomized participants did not receive a dose, whether any participants were excluded from the endpoint analysis, or how those participants were handled.

Missing-data methods for the primary endpoint are not reported in the registry record. In general, missing outcome information can affect an estimated percentage if the likelihood of missingness differs across participants or groups. The record does not explain whether missing outcomes were imputed, treated as failures, excluded, or handled in another way. It also does not provide enough detail to assess sensitivity analyses for missing data.

The registry record does not report interim analyses, stopping rules, the original sample-size justification, or the full statistical analysis plan. These absences limit assessment of how the reported analysis relates to prespecified decisions. The reported endpoint estimates and sponsor analysis can be described as posted, but unreported design and analysis procedures should not be reconstructed from the results.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: acute respiratory failure (12.5%), septic shock (8.3%), acute kidney injury (8.3%), pneumonia bacterial (4.5%), sepsis (4.5%).

The serious-adverse-event figures are counts of participants affected in each arm: 4 of 22 for ibrutinib plus SOC and 3 of 24 for placebo plus SOC. The registry also reports other adverse events in 8 of 22 and 6 of 24, respectively. Deaths are recorded for 1 participant in each arm. These counts describe the posted safety data; they do not establish that an event was caused by study treatment.

The registry lists serious adverse event terms including ACUTE RESPIRATORY FAILURE at 12.5%, SEPTIC SHOCK at 8.3%, ACUTE KIDNEY INJURY at 8.3%, PNEUMONIA BACTERIAL at 4.5%, SEPSIS at 4.5%, and STAPHYLOCOCCAL BACTERAEMIA at 4.5%. The listed percentages should be read as the registry reports them; the denominator and event-specific analysis details are not reported in the record. Some participants may experience more than one event, so event terms should not be added as if they were mutually exclusive participant groups.

Safety counts from a small trial are descriptive and have limited precision. Differences in the counts do not, by themselves, show a causal effect or establish a comparative safety profile. The registry figures do not report all details needed to evaluate event timing, severity grading, relatedness assessments, or exposure-adjusted rates. Those details are not reported in the registry record.

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

The posted primary results describe the proportion of participants alive and without respiratory failure through Day 28 in each randomized arm. The observed percentages were 86.4% for ibrutinib plus SOC and 79.2% for placebo plus SOC. The sponsor’s adjusted difference estimate was 5.8%, but its 95% confidence interval, from -18.1% to 28.7%, includes zero and spans effects in both directions. The unadjusted recalculation likewise has an interval that includes zero.

These results do not establish that one group had a better outcome, nor do they establish that the groups were equivalent. An interval containing zero is compatible with no difference, but it can also be compatible with nonzero differences. Determining equivalence would require a prespecified margin and an appropriate analysis, neither of which is reported in the registry record. The broad intervals and limited arm sizes mean that the estimate is imprecise.

The endpoint combines survival with the absence of a defined respiratory-failure event. A difference in this combined measure would not by itself identify whether survival, respiratory failure, or both accounted for the difference. Separate results for the component outcomes would be needed to understand that distinction. The registry lists mortality and respiratory failure outcomes among its secondary measures, but those outcome names alone do not supply their results.

The trial’s design labels—randomized, quadruple-masked, and parallel-group—describe its structure. They do not remove uncertainty from a small study or answer questions that depend on unreported details, such as missing-data handling, allocation procedures, and multiplicity. The conclusions should remain bounded to the posted participants, endpoint, and analyses.

Nothing in these statistics alone establishes the effect that would be expected in a different population, setting, or treatment context. The registry record describes a completed phase 2 study and its posted primary comparison. It does not report enough information to make broader conclusions about the treatment or to interpret every listed secondary outcome.

17. Why This Trial Matters Statistically

This trial illustrates why an observed difference and the precision of that difference must be considered together. The arm-specific primary outcome percentages are 86.4% and 79.2%, but the sponsor’s adjusted 95% confidence interval for the difference ranges from -18.1% to 28.7%. The point estimate alone gives an incomplete account: the interval shows that the data leave substantial uncertainty about the size and direction of the contrast.

It also illustrates why analysis definitions matter. The sponsor reports an adjusted risk difference using the Miettinen-Nurminen method, while the recalculation compares the posted counts without adjustment. The contrast conventions differ as well. A single phrase such as “risk difference” is not enough to determine whether two estimates can be compared; the groups’ order, the method, and the analysis population all matter.

Finally, the study helps distinguish a trial result from a planning exercise. The sample-size illustrations use fractions of the observed effect under specified assumptions, while the trial’s original design assumptions are not reported in the registry record. Those illustrations are useful for understanding how the required sample size changes when the target effect changes, but they cannot be treated as a record of how the study was planned or as a measure of the completed trial’s power.

More generally, this example highlights the role of transparent reporting. Definitions, analysis populations, missing-data methods, multiplicity procedures, and the rationale for sample size help readers judge how a result was produced and what it can support. Where the registry does not report those details, statistical interpretation must remain appropriately limited.

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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The primary endpoint analysis includes 22 participants in the ibrutinib plus SOC arm and 24 in the placebo plus SOC arm. The resulting confidence intervals are broad, so the estimated difference is imprecise. The planning illustrations based on the observed effect do not explain the trial’s original enrollment target or design; that justification is not reported in the registry record.

The record identifies a Full Analysis Set but does not describe the handling of missing endpoint data, the number of participants with missing assessments, or sensitivity analyses. It also does not report the details of the adjustment in the sponsor’s adjusted risk-difference analysis beyond naming the Miettinen-Nurminen method. Those omissions restrict independent assessment and reproduction of the sponsor’s result.

The registry lists many outcomes and analyses but does not report whether multiplicity was controlled, how secondary analyses were prioritized, or whether interim analyses were performed. It does not report the full statistical analysis plan, allocation-generation and concealment procedures, or which parties were masked. These limits do not negate the posted results, but they constrain evaluation of prespecification and analysis conduct.

The trial concerns a defined adult population with COVID-19 and pulmonary injury and reports a specific endpoint through Day 28. The record does not provide detailed eligibility criteria, baseline characteristics, or information needed to assess how closely the enrolled participants represent other populations. Results for the listed secondary outcomes are not fully described in the registry record reported for the primary comparison, so their effects and precision cannot be assessed from the outcome names alone.

Safety summaries are counts of affected participants and listed terms. The registry record does not include enough detail on event timing, severity, relatedness, or event-specific denominators to support a fuller comparative safety analysis. All these limitations are specific to the information reported for this trial and should be kept distinct from the trial’s observed primary endpoint estimates.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Study of Oral Ibrutinib Capsules to Assess Respiratory Failure in Adult Participants With Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and Pulmonary Injury — NCT04375397.
• Registry record last updated 2022-06-01; status last verified 2022-05.
• Results first posted 2022-06-01.
• 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

NCT04375397 is a completed, randomized, quadruple-masked, parallel-group phase 2 study sponsored by AbbVie. It enrolled 46 participants and compared 420 mg ibrutinib plus standard care with placebo plus standard care, with dosing planned for up to 28 days. The primary endpoint was the percentage alive and without respiratory failure through Day 28.

The posted arm estimates were 86.4% for ibrutinib plus SOC and 79.2% for placebo plus SOC. The sponsor reported an adjusted risk difference of 5.8%, with a 95% confidence interval from -18.1% to 28.7% and a p-value of =0.599. The interval includes zero and is broad. The registry also lists secondary outcomes and safety counts, but the trial’s original sample-size assumptions, missing-data methods, and multiplicity procedures are not reported in the registry record.