The Effect of Enalapril and Losartan on Peritoneal Membrane in Continuous Ambulatory Peritoneal Dialysis Patients

A prospective, randomized, open-label, Single-center clinical trial to determine whether Enalapril or Enalapril plus Losartan effect on Peritoneal membrane transportation.

Study Overview

• Status: Unknown
• Conditions: Continuous Ambulatory Peritoneal Dialysis
• Intervention / Treatment: Drug: Enalapril; Drug: Enalapril plus Losartan; Drug: Placebo

Detailed Description

Detailed description:

Many peritoneal dialysis patients suffer from uremia due to inadequate dialysis or volume overload caused by failure of peritoneal membrane transport.One of the most important etiologies of peritoneal membrane failure are unavoidable to use high glucose-containing dialysate solution that induce injury to mesothelial cell.Previous data found that injured mesothelial cell produces Angiotensin (Ang) II to induce peritoneal inflammation and fibrosis. Blockade of the renin-angiotensin system by angiotensin-converting enzyme inhibition(ACEI) or angiotensin receptor antagonism (ARB) play a major role to slow this effect.

Although many trials in animal study have proved the benefit of ACEI and ARB in peritoneal membrane transport but clinical evidences in human are controversy. Up to now, all previous trials have limitation. First,The trials have small number of population(less than 20 in prospective randomized controlled trial). Second, The trials have multiple confounders on the study population because of the study include old case (that on peritoneal dialysis for many years) and new case (that just start treatment less than 1 year). Third, short duration of study(less than 3 months) to see the significant effect of RAAS blockade on peritoneal membrane transport. Forth, most study use dialysate albumin loss as an index of peritoneal membrane transport ,that less sensitivity to predict peritoneal membrane function. Fifth,no previous trials are attempted to study the effect of combination between ACEI and ARB. Therefore,we design to study the effect of both ACEI and ARB in a larger number of population, only in new case which are just recently found to be on peritoneal dialysis, our study is taken in longer duration and use both modified peritoneal equilibrium test and dialysate CA125 as an index of peritoneal membrane (physiology and anatomic index).This research will demonstrate efficacy of Enalapril and Losartan on Peritoneal membrane transportation lead to improve quality of life in CAPD patients.

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Talerngsak Kanjanabuch, Assist. Prf.; Phone Number: 211 662-2564321; Email: golfnephro@yahoo.com

Study Locations

• Thailand
  • Bangkok, Thailand, 10330
    • Recruiting
    • Chulalongkorn University
    • Contact: Talerngsak Kanjanabuch, Assist. Prf.; Phone Number: 211 662-256-4321; Email: golfnephro@yahoo.com
    • Principal Investigator: Talerngsak Kanjanabuch, Assist. Prf.
    • Sub-Investigator: Wassawon Wontanatawatot, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. All patients received CAPD more than 1 months but less than 1 year
2. Subjects of either sex, more than 20 years old
3. Hypertension
4. Provision of written informed consent by subject or guardian

Exclusion Criteria:

1. No history of taking an ACE inhibitor or angiotensin-receptor blockers or aldosterone antagonist for at least 2 month
2. Serum potassium more than 5.5 mEq/L
3. History of renal artery stenosis
4. Peritonitis or volume overload within the preceding 1 month
5. Myocardial infarction within the preceding 6 months or clinically significant valvular disease or any active cardiovascular disease
6. History of malignant hypertension or hypertensive encephalopathy or cerebrovascular accident within the preceding 6 months
7. Any condition that may have precluded a patient from remaining in the study, such as alcohol or drug abuse, chronic liver disease, malignant disease, or psychiatric disorder
8. History of allergy or intolerance to an ACE inhibitor or ARB
9. Hypotension defined as systolic blood pressure less than 90 mmHg

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Enalapril	Drug: Enalapril; Patients with hypertension will take 20-40mg enalapril per day, antihypertensive agents other than ACE inhibitors and ARBs and spironolactone will be allowed. Doses are adjusted appropriately to achieve and maintain the target blood pressure of 130/80 mmHg; Other Names: Anapril
Active Comparator: Enalapril plus Losartan	Drug: Enalapril plus Losartan; Patients with hypertension will take 20-40mg enalapril plus 25-50mg losartan per day, antihypertensive agents other than ACE inhibitors and ARBs and spironolactone will be allowed. Doses are adjusted appropriately to achieve and maintain the target blood pressure of 130/80 mmHg; Other Names: Anapril plus Loranta
Placebo Comparator: Control; Drug: antihypertensive agents, except ACE inhibitors and ARBs and spironolactone. Administration of antihypertensive agents will select as follows : CCB→β-blocker→α-blocker-->hydralazine	Drug: Placebo; Patients in the control group will administer antihypertensive agents, except ACE inhibitors and ARBs and spironolactone. Doses are adjusted appropriately to achieve and maintain the target blood pressure of 130/80 mmHg; Other Names: Control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in dialysate CA-125 and modified peritoneal equilibrium test	12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Dialysis adequacy, residual renal function, hospitalization, peritonitis episodes, any adverse drug effects, death from any cause	every 1 month, except for dialysis adequacy evaluate every 3 mo

Collaborators and Investigators

• Sponsor: Chulalongkorn University
• Investigators: Principal Investigator: Talerngsak Kanjanabuch, Assist. Prf., Chulalongkorn University

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Anticipated): June 1, 2010
• Study Completion (Anticipated): September 1, 2010

Study Registration Dates

• First Submitted: January 4, 2010
• First Submitted That Met QC Criteria: January 4, 2010
• First Posted (Estimate): January 5, 2010

Study Record Updates

• Last Update Posted (Estimate): May 12, 2010
• Last Update Submitted That Met QC Criteria: May 9, 2010
• Last Verified: May 1, 2010

More Information

Terms related to this study

• Keywords: ACEI; ARB; CAPD; Peritoneal membrane transport
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Enzyme Inhibitors; Protease Inhibitors; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Enalaprilat; Enalapril; Losartan
• Other Study ID Numbers: 203/52