Phase 4 study of evolocumab safety and tolerability in renal transplant recipients

Status: COMPLETED | Phase: PHASE4 Condition(s): Hyperlipidemias Intervention(s): Evolocumab (DRUG) Cardiovascular disease is the leading cause of mortality after renal transplantation, accounting for more than 30% of deaths. Elevated lipid levels (hyperlipidemia) are a frequent finding following transplantation and the immunosuppressive medications play a central role in the development or worsening of hyperlipidemia. In the general population, the correlation between elevated serum cholesterol and increased risk of cardiovascular disease is well established and the reduction in serum LDL cholesterol has proved to significantly reduce both morbidity and mortality. Statin based drugs are the standard of care in the management of hyperlipidemia. Commonly used statin-based drugs include atorvastatin (Lipitor), fluvastatin (Lescol, Lescol XL), lovastatin (Mevacor, Altoprev), pravastatin (Pravachol), rosuvastatin (Crestor), simvastatin (Zocor), and pitavastatin (Livalo). These drugs have been proven to lower lipid levels as well as cardiovascular risk. However, statin-based drugs also cause a variety of side effects. While the most commonly encountered side effects are toxicity to the liver and muscles, a few others have also been known to cause increased excretion of protein in the urine and kidney failure. These side effects are also more common in a renal transplant recipient due to the simultaneous administration of drugs that prevent rejection. Therefore, there is an emergent need for newer drugs which are both efficient and safe especially in this population PCSK-9 inhibitors (Proprotein Convertase Subtilisin Kinase-9 inhibitors) are a new class of drugs that are highly efficient in lowering lipid levels in the general population. However, an exclusive trial involving kidney transplant recipients is yet to be done. Through this study, we would like to evaluate the safety and tolerability of Evolocumab (trade name: Repatha) which is a PCSK-9 inhibitor developed by Amgen, Inc in renal transplant recipients. The study would involve a total of 120 patients across 3 different hospitals in Boston, Massachusetts. Detailed: Cardiovascular disease is the leading cause of death in renal transplant recipients (RTR). 44% of RTR have LDL-C greater than 100mg/dL, six months after transplant. The correlation between the increase in serum LDL level and the increased risk of atherosclerotic cardiovascular disease (ASCVD) is well established. A reduction in LDL level is associated with a decreased risk of mortality and morbidity in patients with ASCVD. Statins have been the long-standing drug of choice in treating dyslipidemia. A single prospective randomized trial known as the ALERT trial compared the benefits of statins to placebo in transplant recipients. The original study consisted of 2000 RTR and an extension of this study evaluated 1652 patients and demonstrated a 21% reduction in major cardiac events (p=0.036) Primary Outcome(s): Percent Change in LDL Cholesterol From Baseline to 12 Months Enrollment: 81 (ACTUAL) Lead Sponsor: Brigham and Women's Hospital Start: 2021-02-17 | Primary Completion: 2024-01-11 Results posted: 2026-04-16