Not Yet RecruitingPhase 3ACTRN12618001124224

FAN Trial: A randomised-controlled trial assessing the effect of lisinopril on Fontan-Associated Nephropathy

Sponsor

Murdoch Children's Research Institute

Enrollment

80 participants

Start Date

Jul 18, 2019

Study Type

Interventional

Conditions

Nephropathy

Summary

Many babies born with a congenital heart condition resulting in only one working heart pumping chamber instead of two undergo a heart operation known as the Fontan procedure. This heart operation enables their heart to function normally however can leave them susceptible to many complications as time goes on, one in particular being kidney damage. There is evidence to suggest (from The ANZ Fontan Registry) that approximately one third of Fontan patients have some degree of kidney damage in the current Australian and New Zealand population. ACEI medications are a class of drugs that have been shown to be effective in improving kidney function and preventing progression of kidney damage, however their effect in Fontan patients is uncertain. This study will evaluate the efficacy of the drug lisinopril, an angiotensin receptor inhibitor (ACEI), on established kidney damage in patients with a Fontan circulation. The main aim of this project is to find out whether initiation of lisinopril is superior to placebo in reducing the degree of kidney damage and preserving kidney function in children and adults with a Fontan circulation. We hypothesise that: 1. Lisinopril initiation will significantly reduce the degree of kidney damage and preserve kidney function after a treatment duration of 6 months. If the hypothesis holds true than it will provide evidence to support the use of ACEI in a subset of Fontan patients with established kidney damage. This would represent a unique group of patients with a clear, testable indication for ACEI therapy after the Fontan procedure. Future implications of this trial would include establishing a model of care for these patients both in terms of screening and treatment of kidney damage and disease hence reducing the burden of this disease for this population group.

Eligibility

Sex: Both males and femalesMin Age: 5 Yearss

Inclusion Criteria4

Participants who:
Are a minimum 5 years of age AND are a minimum of 12-months post Fontan completion (no maximum age)
Live in Victoria or New South Wales 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

Exclusion Criteria11

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
eGFR or GFR <30 ml/min/1.73m2
Bilateral renal artery stenosis
Uncontrolled hypertension
Baseline hyperkalaemia (K > 5.5mmol/L)
Current treatments with potassium sparing diuretics (e.g. spironolactone, amiloride) or NSAIDs (excluding low dose aspirin which is standard of care in many Fontan patients)
Diagnosis of diabetes mellitus
Concurrent use of another experimental drug

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Interventions

The intervention is a once daily dose of lisinopril taken orally for 6 months. All doses greater than 5mg will be in tablet form. However, due to the inability to split tablets, all doses less than 5mg will be administered via dispersion of tablets in a small volume of water (lisinopril is very water soluble). The intervention group will receive lisinopril (APO-lisinopril) at the following doses: • less than 25kg– oral 0.1mg/kg (max 2.5mg) once daily, titrated to a maximum dose of 0.6mg/kg once daily (doses rounded to nearest 0.5mg) Titration for those who weigh less than 25kg will be as follows: commence on 0.1mg/kg once daily, then increase as tolerated to 0.2mg/kg at the 2-week visit, 0.4mg/kg at 4 weeks (phone call), and 0.6mg/kg at the 6-week visit. All doses will be rounded to the nearest 0.5mg. • greater than or equal to 25kg – oral 2.5mg once daily, titrated to a maximum dose of 20mg once daily. Titration for those who weigh greater than or equal to 25kg will be as follows: commence on 2.5mg once daily, then increase as tolerated to 5mg at the 2-week visit, 10mg at 4 weeks (phone call), and 20mg at the 6-week visit. Up-titration will take place over a 6-week period, with patients settling on either the maximum allocated dose or the maximum tolerated dose. Patients will attend a study visit at 2 and 6 weeks. Upward titration at 4 weeks will be conducted via a phone call where patients will be asked about potential side effects of the drug. Dose increase will be made only if study investigators are confident that the patient is not experiencing any significant adverse effects. Patients will then continue on the maximal tolerated dose for a total of 6 months (26 weeks), i.e. from week 6 to week 32. Patients who do not tolerate a total daily dose of 5mg or greater will be excluded from the study. Drug adherence will be measured by a tablet count at each visit. Participants who take greater than or equal to 75% of their pills will be considered to have been compliant and will be included in the final analysis. Participants will also receive a call at 2 and 4 months post randomisation to check medication compliance.