Ignite Creation Date:
2024-05-06 @ 3:20 PM
Last Modification Date:
2024-10-26 @ 1:48 PM
Study NCT ID:
NCT04608474
Status:
RECRUITING
Last Update Posted:
2023-07-27
First Post:
2020-10-12
Brief Title:
Lipid Management in Renal Transplant Recipients Using Evolocumab
Sponsor:
Brigham and Womens Hospital
Organization:
Brigham and Womens Hospital
Study Overview
Official Title:
Lipid Management in Renal Transplant Recipients A Pilot Study Evaluating the Use of PCSK-9 Inhibitor Evolocumab
Status:
RECRUITING
Status Verified Date:
2023-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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
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 Description:
Cardiovascular disease is the leading cause of death in renal transplant recipients RTR 44 of RTR have LDL-C greater than 100mgdL 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 p0036 and a 29 reduction in cardiac death or definite non-fatal myocardial infarction p0014 Even though statins decrease the probability of cardiovascular events there was no difference in graft survival or mortality benefit in RTR Another concerning factor for the use of statins is the tolerability of these drugs Statins have been associated with hepatotoxicity and myotoxicity the incidence of which is higher in RTR This effect is dose-related and may be precipitated by the administration of agents that inhibit cytochrome p450 isoenzymes such as Tacrolimus and Cyclosporine which are the most commonly used immunosuppressants Another statin based drug Fluvastatin has been associated with proteinuria and renal failure Hence there is a need to explore novel treatment options in the management of dyslipidemia particularly in RTR PCSK-9 inhibitors Proprotein Convertase Subtilisin Kinase-9 inhibitors have shown to decrease LDL levels by 60 in patients on statin therapy However these drugs have been studied sparingly in patients with Chronic Kidney Disease CKD and have not yet been analyzed in RTR
The study will involve 120 patients across 3 different hospitals Two different but equivalent drug dosing strategies are available A 420mg monthly subcutaneous injection using an on-body infusor Repatha Pushtronex system or a 140mg subcutaneous injection once every two weeks using a prefilled auto-injector Repatha SureClick The choice of dosing strategy will be based on patient preference This study will be conducted over one year
The study will involve 120 patients across 3 different hospitals Two different but equivalent drug dosing strategies are available A 420mg monthly subcutaneous injection using an on-body infusor Repatha Pushtronex system or a 140mg subcutaneous injection once every two weeks using a prefilled auto-injector Repatha SureClick The choice of dosing strategy will be based on patient preference This study will be conducted over one year
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None