Lipid Management in Renal Transplant Recipients Using Evolocumab.

NCT04608474 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 2020P000437
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 1

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.

Conditions

Hyperlipidemias

Keywords

renal transplant; high cholesterol; hyperlipidemia; cardiovascular disease; Evolocumab; PCSK-9 inhibitors; monoclonal antibody

Outcome Measures

Primary Outcomes (1)

• Percent Change in LDL Cholesterol From Baseline to 12 Months

  The primary efficacy measure is the percent change in LDL cholesterol from baseline to 12 months. The 12-month LDL value is defined as the measurement closest to 12 months within a prespecified window of Months 11 to 13 following treatment initiation. LDL cholesterol is measured in mg/dL.

  Baseline to 12 months (Month 0 to Month 12; assessment window Months 11-13)

Secondary Outcomes (1)

• Absolute Change in LDL Cholesterol From Baseline to 12 Months

  Baseline to 12 months (Month 0 to Month 12; assessment window Months 11-13)

Other Outcomes (1)

• Number of Participants Achieving LDL Cholesterol < 70 mg/dL at Any Time During Follow-up

  From baseline through Month 13

Study Arms (1)

Evolocumab Treatment

EXPERIMENTAL

Participants received evolocumab for lipid lowering.

Drug: Evolocumab

Interventions

Evolocumab DRUG

Two different but equivalent drug dosing strategies are available. A 420mg monthly subcutaneous injection using an on-body infuser (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.

Also known as: Repatha

Evolocumab Treatment

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult renal transplant recipients greater than 1-year post-transplantation, men and women between 18 and 85 years of age, inclusive.
• Any patient with documented ASCVD or diabetes and 1 or more risk factors for ASCVD, including, but not limited to obesity, inactive lifestyle, hypertension, smoking, and family history. and an LDL \>70 mg/dl (Highest-Risk Patients)
• Any patient not classified as one of our highest-risk patients, that has an LDL \>100 mg/dl

You may not qualify if:

• Patients currently enrolled in another interventional clinical trial.
• Patients being actively treated for cellular or antibody-mediated rejection.
• Serious hypersensitivity to Evolocumab or any component of the formulation.
• Patients who are pregnant or planning a pregnancy in the next one year.

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Amgen: collaborator

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (14)

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  PMID: 19191769 BACKGROUND

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  PMID: 1434899 BACKGROUND

• Gaston RS, Kasiske BL, Fieberg AM, Leduc R, Cosio FC, Gourishankar S, Halloran P, Hunsicker L, Rush D, Matas AJ. Use of cardioprotective medications in kidney transplant recipients. Am J Transplant. 2009 Aug;9(8):1811-5. doi: 10.1111/j.1600-6143.2009.02696.x. Epub 2009 Jun 10.

  PMID: 19519808 BACKGROUND

• Cholesterol Treatment Trialists' (CTT) Collaboration; Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, Peto R, Barnes EH, Keech A, Simes J, Collins R. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010 Nov 13;376(9753):1670-81. doi: 10.1016/S0140-6736(10)61350-5. Epub 2010 Nov 8.

  PMID: 21067804 BACKGROUND

• Holdaas H, Fellstrom B, Cole E, Nyberg G, Olsson AG, Pedersen TR, Madsen S, Gronhagen-Riska C, Neumayer HH, Maes B, Ambuhl P, Hartmann A, Staffler B, Jardine AG; Assessment of LEscol in Renal Transplantation (ALERT) Study Investigators. Long-term cardiac outcomes in renal transplant recipients receiving fluvastatin: the ALERT extension study. Am J Transplant. 2005 Dec;5(12):2929-36. doi: 10.1111/j.1600-6143.2005.01105.x.

  PMID: 16303007 BACKGROUND

• Olyaei A, Greer E, Delos Santos R, Rueda J. The efficacy and safety of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors in chronic kidney disease, dialysis, and transplant patients. Clin J Am Soc Nephrol. 2011 Mar;6(3):664-78. doi: 10.2215/CJN.09091010. Epub 2011 Mar 10.

  PMID: 21393488 BACKGROUND

• McKenney JM, Davidson MH, Jacobson TA, Guyton JR; National Lipid Association Statin Safety Assessment Task Force. Final conclusions and recommendations of the National Lipid Association Statin Safety Assessment Task Force. Am J Cardiol. 2006 Apr 17;97(8A):89C-94C. doi: 10.1016/j.amjcard.2006.02.030. Epub 2006 Feb 28.

  PMID: 16581336 BACKGROUND

• Neuvonen PJ, Niemi M, Backman JT. Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance. Clin Pharmacol Ther. 2006 Dec;80(6):565-81. doi: 10.1016/j.clpt.2006.09.003.

  PMID: 17178259 BACKGROUND

• Lemahieu WP, Hermann M, Asberg A, Verbeke K, Holdaas H, Vanrenterghem Y, Maes BD. Combined therapy with atorvastatin and calcineurin inhibitors: no interactions with tacrolimus. Am J Transplant. 2005 Sep;5(9):2236-43. doi: 10.1111/j.1600-6143.2005.01005.x.

  PMID: 16095503 BACKGROUND

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  PMID: 21753749 BACKGROUND

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  PMID: 15027968 BACKGROUND

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• Wanner C, Tonelli M; Kidney Disease: Improving Global Outcomes Lipid Guideline Development Work Group Members. KDIGO Clinical Practice Guideline for Lipid Management in CKD: summary of recommendation statements and clinical approach to the patient. Kidney Int. 2014 Jun;85(6):1303-9. doi: 10.1038/ki.2014.31. Epub 2014 Feb 19.

  PMID: 24552851 BACKGROUND

MeSH Terms

Conditions

Hyperlipidemias; Hypercholesterolemia; Cardiovascular Diseases

Interventions

evolocumab

Condition Hierarchy (Ancestors)

Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Dr. Anil Chandraker
• Organization: Brigham and Women's Hospital

achandraker@bwh.harvard.edu

6177327412

Study Officials

• Anil K Chandraker, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Director, Kidney and Pancreas Transplantation

Model Details: This is a single-arm study in which participants received evolocumab for lipid lowering following renal transplantation. Concomitant statin therapy was permitted based on standard clinical care.

Study Record Dates

• First Submitted: October 12, 2020
• First Posted: October 29, 2020
• Study Start: February 17, 2021
• Primary Completion: January 11, 2024
• Study Completion: May 14, 2025
• Last Updated: April 16, 2026
• Results First Posted: April 16, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)