Clinical trial NCT00602004: Attenuation of Cardiac Effects of Arteriovenous Fistula Creation With Losartan
Official title: Early and Late Cardiac Effects of Arteriovenous Fistula Creation for Haemodialysis in End-stage Renal Failure and Their Possible Attenuation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Renal Failure
Left Ventricular Hypertrophy
Keywords: Arteriovenous fistula
hypertrophy
losartan
Lead sponsor: Melbourne Health
Sponsor class: OTHER
First posted: 2008-01-28
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The primary objective is to determine if the use of losartan, an angiotensin II receptor blocker, can attenuate left ventricular hypertrophy, independent of its antihypertensive effects, in patients with near end stage chronic kidney disease (CKD) who have an arteriovenous fistula created.

Secondary outcomes include the impact of the medication on BNP and hyperkalaemia

Detailed description: Study Design: This is a prospective double blind placebo control 2 arm, randomized (1:1) parallel group study in patients with near end stage renal failure who require creation of an arteriovenous fistula for future haemodialysis. Enrolment will be over a period of 12 months. The blinded phase will be for 3 months. The study design is summarized in Appendix 1. The study consists of a screening phase, a randomization phase and a treatment phase.

Patients will be randomized into 2 groups:

* Group 1 Losartan (50mg daily blinded) and 25 mg of atenolol
* Group 2 Placebo (blinded) and 25 mg of atenolol

Patients: Patients must comply with specified inclusion and exclusion criteria. The number of patients used will be sufficient to show a 15% difference in the left ventricular mass (LVM) between the two groups

Study Endpoints: The primary endpoint is the between group difference in LVM from baseline to 1 month.

Statistical Considerations: The analysis will be based upon an 'ANCOVA'-type linear regression model that includes baseline LVM and treatment group as explanatory variables, and final LVM as the outcome variable.

Eligibility criteria: Inclusion Criteria:

1. Diagnosis of CKD at near-end stage renal failure (CKD Stage IV) ( eGFR = 15-30 mls/min).
2. Age \>18 years of age and \<85 years of age.
3. Males and post-menopausal, sterile women. Non-pregnant pre-menopausal women should be on adequate contraception and have no intention of becoming pregnant during the duration of the study.
4. At baseline TTE LVEF\>45%
5. Willing and able to give informed consent.

Exclusion Criteria:

1. Serum potassium level of more than 5.5 mmol/L
2. Acute myocardial infarction or cerebrovascular accident in the previous 6 months.
3. Severe uncontrolled hypertension (diastolic BP \>100mmHg or systolic BP \>160 mmHg)
4. Evidence or suspicion of renovascular disease.
5. Atrial fibrillation
6. Evidence or suspicion of collagen disease, cancer, psychiatric disorder that interferes with patient compliance, drug or alcohol abuse, pregnancy, breast feeding and ineffective contraception.

Primary outcomes:
measure: left ventricular hypertrophy
timeFrame: 3 months
Secondary outcomes:
Other outcomes:
Locations:
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
Study officials:
affiliation: Melbourne Health
name: Anuradha Aggarwal
role: PRINCIPAL_INVESTIGATOR
affiliation: Melbourne Health
name: Eugenia Pedagogos, FRACP,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zentner D, Pedagogos E, Yapanis A, Karapanagiotidis S, Kinghorn A, Alexiou A, Lee G, Raspudic M, Aggarwal A. Can losartan and blood pressure control peri arteriovenous fistula creation ameliorate the early associated left ventricular hypertrophic response a randomised placebo controlled trial. BMC Res Notes. 2012 May 29;5:260. doi: 10.1186/1756-0500-5-260.