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Published on: April 17, 2021
Comparison of Investigator-Reported and Centrally Adjudicated Heart Failure Outcomes in the EMPEROR-Preserved Trial
Peter Carson1, John R Teerlink2, Michel Komajda3
1Rehoboth Beach, Delaware, USA.
Insights
Investigator adjudication is a reliable alternative to Clinical Events Committees (CECs) for heart failure with preserved ejection fraction (HFpEF) trials, accelerating event collection. Standardized Data Collection for Cardiovascular Trials (SCTI) criteria did not enhance trial performance.
Area of Science:
- Cardiology
- Clinical Trials
- Heart Failure Research
Background:
- Limited data exists on outcome adjudication in heart failure (HF) trials, especially for HF with preserved ejection fraction (HFpEF).
- Accurate outcome adjudication is critical for the integrity of clinical trial results.
Purpose of the Study:
- To compare investigator adjudication with Clinical Events Committee (CEC) adjudication in HFpEF trials.
- To assess the impact of Standardized Data Collection for Cardiovascular Trials (SCTI) criteria on trial outcomes.
Main Methods:
- The study analyzed data from the EMPEROR-Preserved trial.
- Investigator reports were compared with CEC adjudications for concordance and treatment effect.
- The impact of SCTI criteria on heart failure hospitalizations (HHF) and cardiovascular (CV) mortality was evaluated.
Main Results:
- CEC confirmed 67.4% of investigator-reported primary outcome events.
- Treatment effect HRs for the primary outcome and components did not differ between adjudication methods.
- Prognosis after first HHF and total HHFs also showed no significant differences between methods.
- SCTI criteria were present in 92% of CEC HHFs with similar treatment effects.
- Investigator-reported events reached the protocol target 6 months earlier than CEC-adjudicated events.
Conclusions:
- Investigator adjudication offers similar accuracy and faster event accumulation compared to CECs in HFpEF trials.
- Granular SCTI criteria did not improve trial performance.
- A broader definition of HHF events may benefit HFpEF clinical trials.
Background:
There is limited published information on outcome adjudication in heart failure (HF) trials, particularly in heart failure with preserved ejection fraction (HFpEF).
Objectives:
The study sought to compare investigator reports with clinical events committee (CEC) adjudication and assess the impact of the SCTI (Standardized Data Collection for Cardiovascular Trials) criteria.
Methods:
In the EMPEROR-Preserved (EMPagliflozin outcome tRial in Patients with chronic heart Failure With Preserved Ejection Fraction) trial, we compared investigator reports with CEC for concordance, treatment effect on primary composite outcome events and components (first event primary heart failure hospitalization [HHF] or cardiovascular [CV] mortality), prognosis after first HHF, total HHF, and trial duration with and without SCTI criteria.
Results:
The CEC confirmed 67.4% investigator-reported events for the primary outcome (CV mortality 82.7%, HHF 66.3%). The HR for treatment effect did not differ between adjudication methods for the primary outcome: investigator reports (HR: 0.77; 95% CI: 0.69-0.87), CEC (HR: 0.79; 95% CI: 0.69-0.90), its components, or total HHFs. The prognosis after the first HHF for all-cause mortality and CV mortality also did not differ between investigator reports and the CEC, nor did investigator reports and HHFs with a different CEC cause. SCTI criteria were present in 92% of CEC HHFs with a similar treatment effect to non-SCTI criteria. The investigator-reported primary events reached the protocol target number 6 months earlier than the CEC (7 months with full SCTI criteria).
Conclusions:
Investigator adjudication is an alternative to a CEC with similar accuracy and faster event accumulation in HFpEF. The use of granular (SCTI) criteria did not improve trial performance. Our data suggest that a broader definition of an HHF event could be particularly beneficial in HFpEF clinical trials. (EMPagliflozin outcome tRial in Patients with chronic heart Failure With Preserved Ejection Fraction; NCT03057951).
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