The Use of ACE Inhibitors in the Early Renal Post-transplant Period

Chronic allograft nephropathy (CAN) is the leading cause of longterm renal transplant loss. Angiotensin-II may play a role in the development and progression of CAN. Angiotensin converting enzyme inhibitors (ACEI) comprise a drug class that inhibit the effects of angiotensin-II. However these drugs have been reported to cause elevated potassium and creatinine levels in some renal transplant patients. Yet, there are now several retrospective reports of long term benefits of improved renal function and graft survival in renal transplant recipients. There have been no reports of prospective randomized controlled trials of ACEI in renal transplant patients in the early post transplant period.

The purpose of the present study is to assess the safety of enalapril, a drug in the ACEI class, when started 1-3 month post transplant. This is a double-blinded, randomized control trial of enalapril vs. placebo in new renal transplant patients with serum creatinine values no higher than 2.5mg/dl and normal serum potassium levels. The study drug will be administered for 6 months. Patients will be monitored in the renal transplant clinic every 1-4 weeks according to routine protocol. Clinical end-points will be occurence of potassium >5.9mEQ/L or sustained increase in serum creatinine >30% from baseline.

Study Overview

• Status: Completed
• Conditions: Renal Transplant
• Intervention / Treatment: Drug: enalapril; Drug: Placebo

Detailed Description

All new renal transplant recipients with functioning allografts and serum creatinine less than 2.6 mg/dl within the first 3 month post transplant would be eligible for this study of the safety of enalapril 5 mg vs placebo. Patients with serum potassium persistently over 5.5 mEQ/L would be excluded. This is a double-blinded randomized control study. End-points of the study are a persistent rise in serum creatinine of >30% from baseline not otherwise explained by clinical evaluation, and persistent serum potassium >5.9mEQ/L. Study duration is 6 month. At the end of the study patients will be continued on ACEI if clinically stable

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • Bronx, New York, United States, 10467-2490
      • Montefiore Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• New adult renal transplant recipients with good renal function defined as serum creatinine less than 2.6 mg/dl,
• Normal serum potassium levels,
• No contraindication to ACE inhibitor use

Exclusion Criteria:

• Renal transplant patients with persistent serum creatinine levels over 2.5 mg/dl
• Hyperkalemia with serum potassium levels over 5.5 mEQ/dl
• History of allergic reaction to ACE inhibitors or angiotensin receptor blockers
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; 5mg enalapril-matching placebo daily for 6 months
Placebo Comparator: enalapril	Drug: enalapril; 5mg enalapril daily for 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in serum creatinine levels assessed at 6 months	Creatinine is a waste product that comes from the normal wear and tear on muscles of the body. It is excreted through the kidneys. High serum creatinine levels in the blood indicate that the kidneys aren't functioning properly. Increase in serum creatinine of 30% would be a safety concern and requires clinical management.	Baseline and 6 months
Changes in potassium levels assessed at 6 months	Potassium is a chemical that is critical to the function of nerve and muscle cells, including those in your heart. Potassium levels must be kept within a very narrow concentration range. High Potassium levels are a sign of worsening kidney function. An occurence of serum potassium greater than 5.9 mEq/L is a safety concern and requires clinical management.	Baseline and 6 months
Decrease in estimated glomerular filtration rate (eGFR) assessed at 6 months	eGFR is a number based on your blood test for creatinine, a waste product in your blood.It tells how well your kidneys are working. A normal eGFR is 60 or more. A 25 percent decrease in eGFR indicates that the kidneys may not be working well. This is a safety concern and requires clinical management.	Baseline and 6 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cough due to drug intolerance assessed at 6 months	Cough experienced because of inability to tolerate the adverse effects of the medication	Baseline and 6 months
abdominal pain due to drug intolerance assessed at 6 months	Abdominal pain experienced because of inability to tolerate the adverse effects of the medication	Baseline and 6 months
Erythrocytosis assessed at 6 months	Erythrocytosis is a condition in which your body makes too many red blood cells (RBCs). Too many red blood cells can make your blood thicker than normal and lead to blood clots and other complications.	Baseline and 6 months
Leukopenia assessed at 6 months	Leukopenia is a decrease in the number of white blood cells found in the blood, which places individuals at increased risk of infection.	Baseline and 6 months

Collaborators and Investigators

• Sponsor: Montefiore Medical Center
• Investigators: Principal Investigator: Maria Coco, MD, Montefiore Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2004
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: December 23, 2005
• First Submitted That Met QC Criteria: December 23, 2005
• First Posted (Estimate): December 26, 2005

Study Record Updates

• Last Update Posted (Actual): February 7, 2019
• Last Update Submitted That Met QC Criteria: February 5, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: renal transplant, ACE inhibitor
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Protease Inhibitors; Angiotensin-Converting Enzyme Inhibitors; Enalapril
• Other Study ID Numbers: 03-12-311

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No