None listed
Conditions
Brief summary
To evaluate in patients with a Fontan circulation with evidence of nephropathy whether initiation of perindopril erbumine reduces the degree of microalbuminuria compared to controls as measured by a spot urine albumin-creatinine ratio over 6 months of treatment.
Interventions
This is a prospective, multi-centre, randomised-controlled trial of perindopril erbumine versus non-intervention in children and adults with a Fontan circulation and evidence of established nephropathy defined as an elevated urine albumin-creatinine ratio (>2.5mg/mmol in males and >3.5mg/mmol in females), and/or a reduced GFR (<90ml/min/1.73m2). Eligible participants will be randomised to receive either perindopril erbumine or no intervention, with stratification based on sex and age (<18 or >=1
This is a prospective, multi-centre, randomised-controlled trial of perindopril erbumine versus non-intervention in children and adults with a Fontan circulation and evidence of established nephropathy defined as an elevated urine albumin-creatinine ratio (>2.5mg/mmol in males and >3.5mg/mmol in females), and/or a reduced GFR (<90ml/min/1.73m2). Eligible participants will be randomised to receive either perindopril erbumine or no intervention, with stratification based on sex and age (<18 or >=18). Dosage and route of administration Group A will receive the ACE inhibitor perindopril erbumine taken orally at the following doses: <25kg– oral tablet 1mg once daily, titrated to a maximum dose of 2mg once daily =/>25kg – oral tablet 2mg once daily titrated to a maximum dose of 4mg once daily Dose tolerance will be checked at visit 2 (2 weeks) and up-titrated only if study investigators are confident that the participant is not experiencing any significant adverse effects. Participants will not be titrating the dose themselves. Titration for those <25kg will be as follows: commence on 1mg once daily, then increase as tolerated to 2mg at the 2-week visit. Titration for those =25kg will be as follows: commence on 2mg once daily, then increase as tolerated to 4mg at the 2-week visit. Participants will then continue on the maximum tolerated dose for a total of 26 weeks, i.e., from week 2 to week 28 post-randomisation. Participants who do not tolerate a total daily dose of 2mg or greater (1mg in those <25 kg) will be excluded from the study.
Sponsors
Australian Heart Foundation
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Prevention
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
5 Years to No maximum
Healthy volunteers
No
Inclusion criteria
• Are a minimum 5 years of age at the time of screening AND are a minimum of 12-months post Fontan completion (no maximum age) • Live within Auckland or within 2-3 hour drive of Auckland, NZ or in New South Wales, Australia and can attend multiple study visits at the closest respective centre. • Are not currently taking an ACE inhibitor or ARB, nor have taken a medication belonging to either of these two classes for greater than 7 consecutive days within the last 3 months prior to screening urine sample. • Evidence of established nephropathy defined as an elevated urine albumin-creatinine ratio (>2.5mg/mmol in males and >3.5mg/mmol in females) and/or GFR 30-90 ml/min/1.73m2 • Are up-to-date with vaccinations based on the countrywide, accepted schedule of childhood vaccines, including Covid-19 prevention
Exclusion criteria
• Currently pregnant or have been pregnant within the past 12 months beyond the first trimester (13 weeks), (identified at initial phone call). • Of child-bearing potential with ineffective contraception. • Currently breastfeeding. • Known hypersensitivity or intolerance to ACE inhibitors • Currently on lithium or requiring high doses of diuretics • eGFR or GFR <30 ml/min/1.73m2 (pre-existing, or identified at baseline) • Known bilateral renal artery stenosis • Known uncontrolled hypertension • Moderate or greater systemic ventricular dysfunction on most recent echocardiogram • Baseline hyperkalaemia (K > 5.5mmol/L in a non-haemolysed sample) • Current treatments with regular non-steroidal anti-inflammatory drugs (NSAIDs) (excluding low dose aspirin which is standard of care in many Fontan patients) • Diagnosis of diabetes mellitus • Concurrent use of another experimental drug • Participants who currently require surgical intervention or are anticipated to require surgical intervention relating to their Fontan circulation during the time period of the study. • Children unable to swallow tablets
Outcome results
None listed