Effects of Angiotensin Converting Enzyme Inhibitors on Patency of Arterio-Venous Fistulas: A Randomized Controlled Trial
Status:
Recruiting
Trial end date:
2022-09-30
Target enrollment:
Participant gender:
Summary
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.
Phase:
Early Phase 1
Details
Lead Sponsor:
Armed Forces Post Graduate Medical Institute (AFPGMI), Rawalpindi