drugset / Trial / NCT02924727
Prospective ARNI vs ACE Inhibitor Trial to DetermIne Superiority in Reducing Heart Failure Events After MI
RandomizedParallel-groupQuadruple-blindTreatment
Summary
The purpose of this study is to evaluate the efficacy and safety of LCZ696 titrated to a target dose of 200 mg twice daily, compared to ramipril titrated to a target dose of 5 mg twice daily.
Timeline
- Start
- 2016-12-09
- Primary completion
- 2021-02-26
- Completion
- 2021-02-26
Outcome
Missed primary endpoint
registry analysis (superiority test); LCZ696 (Sacubitril/Valsartan) vs Ramipril; p = 0.1659; Hazard Ratio (HR) 0.9012 (95% CI 0.7778 to 1.0441); Cox's Proportional Hazard Model NCT02924727 ↗
release “the Ph3 PARADISE-MI study did not meet its primary composite endpoint of reducing risk of cardiovascular death and heart failure events after an acute myocardial infarction.” novartis.com ↗
Publications
- Curtain JP, Pfeffer MA, Braunwald E, Claggett BL, Granger CB, Kober L, Lewis EF, Maggioni AP, Mann DL, Rouleau JL, Solomon SD, Steg PG, Finn PV, Fernandez A, Jering KS, McMurray JJV. Rates of Sudden Death After Myocardial Infarction-Insights From the VALIANT and PARADISE-MI Trials. JAMA Cardiol. 2024 Oct 1;9(10):928-933. doi: 10.1001/jamacardio.2024.2356.
- Mann DL, Nicolas J, Claggett B, Miao ZM, Granger CB, Kerkar P, Kober L, Lewis EF, McMurray JJV, Maggioni AP, Nunez J, Ntsekhe M, Rouleau JL, Sim D, Solomon SD, Steg PG, van der Meer P, Braunwald E, Pfeffer MA, Mehran R. Angiotensin Receptor-Neprilysin Inhibition in Patients With STEMI vs NSTEMI. J Am Coll Cardiol. 2024 Mar 5;83(9):904-914. doi: 10.1016/j.jacc.2024.01.002.
- Petrie MC, Rouleau JL, Claggett B, Jering K, van der Meer P, Kober L, Miao ZM, Lewis E, Granger C, De Pasqulae CG, Mann D, Steg PG, Maggioni A, Amir O, Lefkowitz M, Braunwald E, Solomon SD, McMurray JJV, Pfeffer MA. Pulmonary Congestion and Left Ventricular Dysfunction After Myocardial Infarction: Insights From the PARADISE-MI Trial. Circulation. 2024 Jan 23;149(4):335-338. doi: 10.1161/CIRCULATIONAHA.123.066163. Epub 2024 Jan 22. No abstract available.
- Schou M, Claggett B, Miao ZM, Fernandez A, Filippatos G, Granger C, Jering K, Maggioni AP, McCausland F, Villota JN, Rouleau JL, Mody FV, van der Meer P, Vinereanu D, McGrath M, Zhou Y, Mann DL, Solomon SD, Steg PG, Braunwald E, McMurray JJV, Pfeffer MA, Kober L. Sacubitril/valsartan compared to ramipril in high-risk post-myocardial infarction patients stratified according to use of mineralocorticoid receptor antagonists: Insight from the PARADISE MI trial. Eur J Heart Fail. 2024 Jan;26(1):130-139. doi: 10.1002/ejhf.3079. Epub 2023 Nov 29.
- Wang X, Jering KS, Cikes M, Tokmakova MP, Mehran R, Han Y, East C, Mody FV, Wang Y, Lewis EF, Claggett B, McMurray JJV, Granger CB, Pfeffer MA, Solomon SD. Sex Differences in Clinical Characteristics and Outcomes After Myocardial Infarction With Low Ejection Fraction: Insights From PARADISE-MI. J Am Heart Assoc. 2023 Sep 5;12(17):e028942. doi: 10.1161/JAHA.122.028942. Epub 2023 Aug 23.
- Jering KS, Claggett BL, Pfeffer MA, Granger CB, Kober L, Lewis EF, Maggioni AP, Mann DL, McMurray JJV, Prescott MF, Rouleau JL, Solomon SD, Steg PG, von Lewinski D, Braunwald E. Prognostic Importance of NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) Following High-Risk Myocardial Infarction in the PARADISE-MI Trial. Circ Heart Fail. 2023 May;16(5):e010259. doi: 10.1161/CIRCHEARTFAILURE.122.010259. Epub 2023 May 1.
- Mehran R, Steg PG, Pfeffer MA, Jering K, Claggett B, Lewis EF, Granger C, Kober L, Maggioni A, Mann DL, McMurray JJV, Rouleau JL, Solomon SD, Ducrocq G, Berwanger O, De Pasquale CG, Landmesser U, Petrie M, Leng DSK, van der Meer P, Lefkowitz M, Zhou Y, Braunwald E. The Effects of Angiotensin Receptor-Neprilysin Inhibition on Major Coronary Events in Patients With Acute Myocardial Infarction: Insights From the PARADISE-MI Trial. Circulation. 2022 Dec 6;146(23):1749-1757. doi: 10.1161/CIRCULATIONAHA.122.060841. Epub 2022 Nov 2.
- Shah AM, Claggett B, Prasad N, Li G, Volquez M, Jering K, Cikes M, Kovacs A, Mullens W, Nicolau JC, Kober L, van der Meer P, Jhund PS, Ibram G, Lefkowitz M, Zhou Y, Solomon SD, Pfeffer MA. Impact of Sacubitril/Valsartan Compared With Ramipril on Cardiac Structure and Function After Acute Myocardial Infarction: The PARADISE-MI Echocardiographic Substudy. Circulation. 2022 Oct 4;146(14):1067-1081. doi: 10.1161/CIRCULATIONAHA.122.059210. Epub 2022 Sep 9.
- Pfeffer MA, Claggett B, Lewis EF, Granger CB, Kober L, Maggioni AP, Mann DL, McMurray JJV, Rouleau JL, Solomon SD, Steg PG, Berwanger O, Cikes M, De Pasquale CG, Fernandez A, Filippatos G, Jering K, Landmesser U, Menon V, Merkely B, Petrie MC, Petrov I, Schou M, Senni M, Sim D, van der Meer P, Lefkowitz M, Zhou Y, Wang Y, Braunwald E. Impact of Sacubitril/Valsartan Versus Ramipril on Total Heart Failure Events in the PARADISE-MI Trial. Circulation. 2022 Jan 4;145(1):87-89. doi: 10.1161/CIRCULATIONAHA.121.057429. Epub 2021 Nov 19. No abstract available.
- Pfeffer MA, Claggett B, Lewis EF, Granger CB, Kober L, Maggioni AP, Mann DL, McMurray JJV, Rouleau JL, Solomon SD, Steg PG, Berwanger O, Cikes M, De Pasquale CG, East C, Fernandez A, Jering K, Landmesser U, Mehran R, Merkely B, Vaghaiwalla Mody F, Petrie MC, Petrov I, Schou M, Senni M, Sim D, van der Meer P, Lefkowitz M, Zhou Y, Gong J, Braunwald E; PARADISE-MI Investigators and Committees. Angiotensin Receptor-Neprilysin Inhibition in Acute Myocardial Infarction. N Engl J Med. 2021 Nov 11;385(20):1845-1855. doi: 10.1056/NEJMoa2104508.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | LCZ696 | Unknown | 50 mg | — |
| Subject | LCZ696 | Unknown | 100 mg | — |
| Subject | LCZ696 | Unknown | 200 mg | — |
| Comparator | Ramipril | Small molecule | 1.25 mg | Oral |
| Comparator | Ramipril | Small molecule | 2.5 mg | Oral |
| Comparator | Ramipril | Small molecule | 5 mg | Oral |
| Background | Valsartan | Unknown | 40 mg | — |
| Background | Valsartan | Unknown | 80 mg | — |