Effects of Angiotensin Converting Enzyme Inhibitors on Patency of Arterio-Venous Fistulas: A Randomized Controlled Trial

Chronic kidney disease (CKD) is one of the leading health problems imbibing a major portion of health budget worldwide. The global prevalence of CKD is estimated to be 13.4% with approximately 5 to 7 million people needing renal replacement therapy. There is lack of epidemiological surveys regarding CKD but it is estimated to be around 5% and nearly half of them are diabetic. In Pakistan most of the patients undergo hemodialysis as mode of renal replacement as renal transplant centers are few and over burdened. Therefore, a good vascular access for hemodialysis is vital for CKD patients. A functioning arterio-venous fistula (AVF) improves quality of life and morbidity. However, access failure remains a major problem in patients of CKD accounting for third most common cause of admission. There are various options for attaining vascular access but AVF remains the most reliable with less morbidity and better overall patency rate. However, the AVF has its own limitation and has overall patency rate of 50-70% at 1 year and 30-40% at 2 years. This outcome indicates that strategies to prevent occlusion by altering modifiable risk factors are suboptimal and warrant further research.

Patients of CKD often have associated cardiovascular diseases as Ischemic heart disease, left ventricular failure and angina. They are often taking cardio-protective medicines as antiplatelets, angiotensin converting enzymes and calcium channel blockers. Intimal hyperplasia has been shown to be the most important cause of AVF failures.2 Angiotensin II promotes vascular smooth muscle proliferation through various growth factors. Various experimental models have clearly depicted that ACE inhibitors effectively stop smooth muscle growth and intimal hyperplasia in vessel walls. Literature review shows conflicting results in terms of AVF patency when ACE inhibitors are used in conjunction. A study by Jackson RS and colleagues showed that ACE inhibitor were associated with reduced hazard ratio [HR], 0.35; 95% confidence interval [CI], 0.16-0.76; P = .008). Whereas, another study showed no role of ACE inhibitors in preventing graft failure. The possible explanation can be study designs as most studies were retrospective and effects of possible confounders. Moreover, there is lack of research in Pakistan to see the effects of pharmacological drugs on primary patency of AVF among CKD patients.

The rationale of this study is to effectively establish the role of ACE inhibitors in achieving primary patency of AV fistulas while reducing the number of confounders. This will be the first randomized controlled trial conducted in Pakistan. The primary outcome is AVF patency at one year. Secondary outcomes will include graft complications and graft maturation time after surgery.

Study Overview

• Status: Recruiting
• Conditions: Vascular Access Complication
• Intervention / Treatment: Drug: Losartan Potassium; Drug: multi-vitamins

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Pakistan
  • Punjab
    • Rawalpindi, Punjab, Pakistan, 46000
      • Recruiting
      • Anas Bin Saif
      • Contact: Anas Saif; Phone Number: 00923341115343; Email: anasbinsaif02@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

All patients who were undergoing Hemodialysis or were intended to start HD within three months between the age of 20 years to 70 years were included in the study

Exclusion Criteria:

• Age less than 20 years or more than 79 years
• In patients who are not expected to start dialysis in next 3 months
• Non-consenting patients
• Patients with diagnosed carcinoma whose life expectancy is less than a year.
• Patients with un-controlled hypertension on multiple regimes of antihypertensive
• Patients allergic to ACE inhibitors

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Use of ACE inhibitor; losartan potassium will be administered 25 mg daily	Drug: Losartan Potassium; ACE inhibitor
Placebo Comparator: placebo group; matched for age and gender	Drug: multi-vitamins; placebo drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
primary patency at one year	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
graft complications	1 year
maturation time of fistula	1 year

Collaborators and Investigators

• Sponsor: Armed Forces Post Graduate Medical Institute (AFPGMI), Rawalpindi

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2021
• Primary Completion (Anticipated): September 30, 2022
• Study Completion (Anticipated): September 30, 2022

Study Registration Dates

• First Submitted: November 22, 2021
• First Submitted That Met QC Criteria: November 22, 2021
• First Posted (Actual): November 24, 2021

Study Record Updates

• Last Update Posted (Actual): November 24, 2021
• Last Update Submitted That Met QC Criteria: November 22, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Congenital Abnormalities; Pathological Conditions, Anatomical; Cardiovascular Abnormalities; Vascular Malformations; Arteriovenous Malformations; Vascular Fistula; Fistula; Arteriovenous Fistula; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Losartan
• Other Study ID Numbers: 105471

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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