drugset / Trial / NCT02586155
Effect of RVX000222 on Time to Major Adverse Cardiovascular Events in High-Risk T2DM Subjects With CAD
Phase 3
Completed
2425 enrolled
Resverlogix Corp
ICON plc · collabMedidata Solutions · collabPPD Development, LP · collab
RandomizedParallel-groupTriple-blindPrevention
Summary
The purpose of this study is to determine whether bromodomain extraterminal domain (BET) inhibition treatment with RVX000222 in high-risk type 2 diabetes mellitus patients with coronary artery disease increases the time to major adverse cardiovascular events.
Timeline
- Start
- 2015-11
- Primary completion
- 2020-11-30
- Completion
- 2021-06-21
Outcome
Missed primary endpoint
registry analysis (superiority test); High-Intensity Statin Therapy+RVX000222 vs High-Intensity Statin Therapy+Placebo; p = 0.1070; Cox Proportional Hazard 0.823 (95% CI 0.649 to 1.044); Stratified long-rank NCT02586155 ↗
paper the selective bromodomain and extraterminal protein inhibitor apabetalone added to standard therapy did not significantly reduce the risk of major adverse cardiovascular events. PMID 32219359 ↗
Publications
- Results Ray KK, Nicholls SJ, Buhr KA, Ginsberg HN, Johansson JO, Kalantar-Zadeh K, Kulikowski E, Toth PP, Wong N, Sweeney M, Schwartz GG; BETonMACE Investigators and Committees. Effect of Apabetalone Added to Standard Therapy on Major Adverse Cardiovascular Events in Patients With Recent Acute Coronary Syndrome and Type 2 Diabetes: A Randomized Clinical Trial. JAMA. 2020 Apr 28;323(16):1565-1573. doi: 10.1001/jama.2020.3308.
- Schwartz GG, Nicholls SJ, Toth PP, Sweeney M, Halliday C, Johansson JO, Wong NCW, Kulikowski E, Kalantar-Zadeh K, Ginsberg HN, Ray KK. Relation of insulin treatment for type 2 diabetes to the risk of major adverse cardiovascular events after acute coronary syndrome: an analysis of the BETonMACE randomized clinical trial. Cardiovasc Diabetol. 2021 Jun 22;20(1):125. doi: 10.1186/s12933-021-01311-9.
- Haarhaus M, Gilham D, Kulikowski E, Magnusson P, Kalantar-Zadeh K. Pharmacologic epigenetic modulators of alkaline phosphatase in chronic kidney disease. Curr Opin Nephrol Hypertens. 2020 Jan;29(1):4-15. doi: 10.1097/MNH.0000000000000570.
- Ray KK, Nicholls SJ, Ginsberg HD, Johansson JO, Kalantar-Zadeh K, Kulikowski E, Toth PP, Wong N, Cummings JL, Sweeney M, Schwartz GG. Effect of selective BET protein inhibitor apabetalone on cardiovascular outcomes in patients with acute coronary syndrome and diabetes: Rationale, design, and baseline characteristics of the BETonMACE trial. Am Heart J. 2019 Nov;217:72-83. doi: 10.1016/j.ahj.2019.08.001. Epub 2019 Aug 9.
- Gilham D, Tsujikawa LM, Sarsons CD, Halliday C, Wasiak S, Stotz SC, Jahagirdar R, Sweeney M, Johansson JO, Wong NCW, Kalantar-Zadeh K, Kulikowski E. Apabetalone downregulates factors and pathways associated with vascular calcification. Atherosclerosis. 2019 Jan;280:75-84. doi: 10.1016/j.atherosclerosis.2018.11.002. Epub 2018 Nov 14.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Apabetalone | Small molecule | 100 mg | Oral |
| Background | Atorvastatin | Small molecule | — | — |
| Background | Rosuvastatin | Small molecule | — | — |