The Use of ACE Inhibitors in the Early Renal Post-transplant Period
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: enalapril
|
Drug: enalapril
5mg enalapril daily for 6 months
|
| Placebo Comparator: Placebo
|
Drug: Placebo
5mg enalapril-matching placebo daily for 6 months
|
Outcome Measures
Primary Outcome Measures
- Changes in serum creatinine levels assessed at 6 months [Baseline and 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.
- Changes in potassium levels assessed at 6 months [Baseline and 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.
- Decrease in estimated glomerular filtration rate (eGFR) assessed at 6 months [Baseline and 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.
Secondary Outcome Measures
- Cough due to drug intolerance assessed at 6 months [Baseline and 6 months]
Cough experienced because of inability to tolerate the adverse effects of the medication
- abdominal pain due to drug intolerance assessed at 6 months [Baseline and 6 months]
Abdominal pain experienced because of inability to tolerate the adverse effects of the medication
- Erythrocytosis assessed at 6 months [Baseline and 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.
- Leukopenia assessed at 6 months [Baseline and 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.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Montefiore Medical Center | Bronx | New York | United States | 10467-2490 |
Sponsors and Collaborators
- Montefiore Medical Center
Investigators
- Principal Investigator: Maria Coco, MD, Montefiore Medical Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 03-12-311