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CARDIOVAX-HF Phase III Trial Exhibit

Evaluation of Cardiovax (novel dual ARNI/SGLT2-mimetic) in Heart Failure with Reduced Ejection Fraction (HFrEF).

Phase III Superiority RCT ITT Population: n = 4,744
Exhibit Section 1: Study Abstract & Trial Design Double-Blind RCT

Protocol: Multicenter, Event-Driven Superiority Trial

Objective: To assess whether Cardiovax (100 mg daily) plus standard guideline-directed medical therapy (GDMT) reduces cardiovascular mortality and heart failure hospitalizations compared to matched placebo plus GDMT in ambulatory patients with NYHA class II–IV HFrEF and LVEF ≤ 35%.

Randomization 1:1 Permuted Block Stratified by baseline NT-proBNP
Power & Significance Power = 90% (β = 0.10) Two-sided α = 0.05 threshold
Median Follow-up 28.4 Months Loss to follow-up < 0.4%
Exhibit Section 2: Time-to-Event Analysis Primary Composite Endpoint

Kaplan-Meier Cumulative Event Rates Over 36 Months

Composite of CV Death or Urgent Heart Failure Hospitalization.

25% 20% 15% 10% 0% 0m 12m 24m 36m Placebo + GDMT (21.2% at 36m) Cardiovax + GDMT (16.3% at 36m) HR: 0.74 (95% CI: 0.65–0.85) Log-Rank p < 0.0001 (Superiority)
Patients at Risk: 0m12m24m36m
Cardiovax (n = 2,373): 2,3732,2582,0841,821
Placebo (n = 2,371): 2,3712,1901,9621,685
Exhibit Section 3: Clinical Endpoints Matrix Intention-to-Treat (ITT) Analysis

Primary, Secondary & Safety Out-comes

Endpoint Cardiovax (n=2373) Placebo (n=2371) Hazard Ratio (95% CI) p-value
Primary Composite (CV Death or HF Hosp) 386 (16.3%) 502 (21.2%) 0.74 (0.65–0.85) <0.001
First Hospitalization for Heart Failure 231 (9.7%) 318 (13.4%) 0.70 (0.59–0.83) <0.001
Cardiovascular Death (Isolated) 227 (9.6%) 273 (11.5%) 0.82 (0.69–0.98) 0.029
All-Cause Mortality 276 (11.6%) 312 (13.2%) 0.87 (0.74–1.02) 0.082 (NS)
Symptomatic Hypotension (Adverse Event) 142 (6.0%) 83 (3.5%) 1.74 (1.33–2.28) <0.001
COMLEX / USMLE Board Item Interactive Test Mode

Based on the CARDIOVAX-HF trial exhibit above, which of the following represents the correct Number Needed to Treat (NNT) to prevent one primary composite event over 36 months, and what is the primary methodological reason for reporting Intention-to-Treat (ITT) rather than Per-Protocol analysis?

A. NNT = 14; ITT analysis maximizes statistical power by including only fully compliant patients who completed all 36 months of therapy.
B. NNT = 21 (rounded up); ITT analysis preserves the baseline prognostic balance generated by randomization and reflects real-world clinical effectiveness by avoiding attrition bias.
C. NNT = 21; ITT analysis evaluates drug efficacy under idealized conditions by removing all non-compliant individuals and protocol violators.
D. NNT = 49; Per-protocol analysis is preferred because it guarantees elimination of confounding variables and selection bias.
E. NNT = 74; ITT analysis is required by regulatory agencies solely because it increases the Hazard Ratio relative to observational registries.
✔ Psychometric Rationale & Formula Breakdown:

1. NNT Calculation:
Control Event Rate (CER) = 21.2% (0.212)
Experimental Event Rate (EER) = 16.3% (0.163)
Absolute Risk Reduction (ARR) = CER - EER = 21.2% - 16.3% = 4.9% (0.049)
NNT = 1 / ARR = 1 / 0.049 = 20.41 → Always round UP to the nearest whole integer: NNT = 21 patients.

2. ITT vs. Per-Protocol Analysis:
Intention-to-treat analyzes patients according to their randomized assignment regardless of adherence, dropouts, or cross-overs. This maintains prognostic comparability between arms, prevents attrition bias, and yields an estimate of clinical effectiveness. Per-protocol analysis assesses only compliant subjects, introducing substantial post-randomization selection bias.