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

Sponsor

Chulalongkorn University (Other)

Overall Status

Unknown status

CT.gov ID

NCT01041963

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Continuous Ambulatory Peritoneal Dialysis	Drug: Enalapril Drug: Enalapril plus Losartan Drug: Placebo	Phase 4

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 Design

Study Type:

Interventional

Anticipated Enrollment :

90 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

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

Study Start Date :

Jun 1, 2009

Anticipated Primary Completion Date :

Jun 1, 2010

Anticipated Study Completion Date :

Sep 1, 2010

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Change in dialysate CA-125 and modified peritoneal equilibrium test [12 months]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

No history of taking an ACE inhibitor or angiotensin-receptor blockers or aldosterone antagonist for at least 2 month
Serum potassium more than 5.5 mEq/L
History of renal artery stenosis
Peritonitis or volume overload within the preceding 1 month
Myocardial infarction within the preceding 6 months or clinically significant valvular disease or any active cardiovascular disease
History of malignant hypertension or hypertensive encephalopathy or cerebrovascular accident within the preceding 6 months
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
History of allergy or intolerance to an ACE inhibitor or ARB
Hypotension defined as systolic blood pressure less than 90 mmHg