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

This is a prospective, randomized, placebo controlled, multi-center clinical trial to determine whether aliskiren or aliskiren plus losartan or enalapril plus losartan effects on peritoneal membrane transportation.

Study Overview

• Status: Unknown
• Conditions: Peritoneal Membrane Failure
• Intervention / Treatment: Drug: Aliskiren; Drug: Aliskiren plus Losartan; 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 transportation. One of the most important etiologies of peritoneal membrane failure is unavoidable to use high glucose-containing dialysate solution that induces injury to mesothelial cells. Previous data found that injured mesothelial cell produced Angiotensin II inducing peritoneal inflammation and fibrosis. Blockade of the renin-angiotensin system by angiotensin-converting enzyme inhibition or angiotensin receptor antagonism play a major role to slow these effects.

Many trials in animal studies have proved the benefit of angiotensin-converting enzyme inhibition and angiotensin receptor antagonism in preservation of peritoneal membrane but clinical evidences in human are controversy in the past. Recently our data have demonstrated the roles of angiotensin-converting enzyme inhibition and angiotensin receptor antagonism for slowing peritoneal membrane dysfunction in views of anatomy and solute transportation (abstract presentation in American Society of Nephrology 2010). These available data confirmed that renin-angiotensin system blockages were benefit. Nowadays, there is a new class of antihypertensive drug, called direct renin inhibitor . It blocks (pro)renin active site that is the rate- limiting step of renin-angiotensin system. We're interesting in this drug and wonder it can slow the peritoneal membrane dysfunction in continuous ambulatory peritoneal dialysis patients. Therefore, we design a study to show the effect of aliskiren alone or combination with angiotensin receptor antagonism for slowing peritoneal membrane dysfunction in naive continuous ambulatory peritoneal dialysis patients in several hospitals. Our study will be taken in 1 year duration and uses modified peritoneal equilibrium test and dialysate cancer antigen 125 (CA125) as indexes of peritoneal membrane transportations.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 4

Contacts and Locations

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

Study Locations

• Thailand
  • Bangkok, Thailand, 10330
    • Recruiting
    • Chulalongkorn University
    • Principal Investigator: Talerngsak Kanjanabuch, Assist. Prf.
    • Contact: Talerngsak Kanjanabuch, Assist. Prf.; Phone Number: 211 662-2564321; Email: golfnephro@hotmail.com
    • Sub-Investigator: Pichaya Tantiyavarong, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. All patients received continuous ambulatory peritoneal dialysis less than one and a half years
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 angiotensin converting enzyme 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 angiotensin converting enzyme inhibitors or angiotensin receptor blockers
9. Hypotension defined as systolic blood pressure less than 90 mmHg

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo	Drug: placebo; Patients in the control group will administer antihypertensive agents, except angiotensin converting enzyme inhibitors, angiotensin receptor blockers and spironolactone. Dosages are adjusted appropriately to achieve and maintain the target blood pressure of 130/80 mmHg; Other Names: Control
Active Comparator: Aliskiren	Drug: Aliskiren; Patients with hypertension will take fixed-dose 150 mg aliskiren per day. Antihypertensive agents other than angiotensin converting enzyme inhibitors, angiotensin receptor blocker and spironolactone will be allowed and dosages are adjusted appropriately to achieve and maintain the target blood pressure of 130/80 mmHg; Other Names: Aliskiren group
Active Comparator: Enalapril plus Losartan	Drug: Enalapril plus Losartan; Patients with hypertension will take fixed-dose 20 mg enalapril + 50 mg losartan per day. Antihypertensive agents other than angiotensin converting enzyme inhibitors, angiotensin receptor blockers and spironolactone will be allowed and dosages are adjusted appropriately to achieve and maintain the target blood pressure of 130/80 mmHg; Other Names: Enalapril plus Losartan group
Active Comparator: Aliskiren plus Losartan	Drug: Aliskiren plus Losartan; Patients with hypertension will take fixed-dose 150 mg aliskiren + 50 mg losartan per day. Antihypertensive agents other than angiotensin converting enzyme inhibitors, angiotensin receptor blockers and spironolactone will be allowed and dosages are adjusted appropriately to achieve and maintain the target blood pressure of 130/80 mmHg; Other Names: Aliskiren plus Losartan group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changing in modified peritoneal equilibrium test	Modified peritoneal equilibrium test is the standard test for evaluation peritoneal membrane transportation.	at the beginning, 6 months and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
appearance rate of dialysate CA125	Appearance rate of dialysate CA125 refers to anatomical change of peritoneal. It can be calculated by multiplying dialysate CA125 with dialysate volume and deviding by dwell time.	the begining, 6 months and 12 months
nutritional status	assess by serum albumin and subjective global assessment	at the beginning, 6 months and 12 months
adverse events	adverse events of the drugs	12 months

Collaborators and Investigators

• Sponsor: Chulalongkorn University
• Investigators: Principal Investigator: Talerngsak Kanjanabuch, Assist. Prf., Investigator; Study Director: Pichaya Tantiyavarong, MD., Chulalongkorn University

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Anticipated): August 1, 2011
• Study Completion (Anticipated): October 1, 2011

Study Registration Dates

• First Submitted: November 30, 2010
• First Submitted That Met QC Criteria: February 28, 2011
• First Posted (Estimate): March 1, 2011

Study Record Updates

• Last Update Posted (Estimate): March 10, 2011
• Last Update Submitted That Met QC Criteria: March 8, 2011
• Last Verified: February 1, 2011

More Information

Terms related to this study

• Keywords: Aliskiren; Losartan; Peritoneal membrane dysfunction
• 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: 162/53