Indapamide treatment for heart failure - a pilot study
Treatment of heart failure using indapamide : a pilot study of its effect on plasma FGF23
Leong L Ng
University of Leicester
Duration of Study in the UK
1 years, 6 months, 1 days
Heart failure patients can have reduced or normal heart muscle contraction. Whilst treatments for reduced contraction have been developed, there are few treatments for patients with normal muscle contraction. Such patients are often older females with high blood pressure who often have stiff hearts. We have found patients with heart failure often have high levels of one particular growth factor (fibroblast growth factor 23, FGF23) that causes heart muscle thickening. We wish to test a drug that is used to treat high blood pressure (indapamide) in patients with heart failure, to see if it affects the blood levels of factors that influence heart muscle thickening. This is a pilot study, involving giving heart failure patients indapamide, and observing the levels of the blood factors over 8 weeks. Patients will be attending on 4 occasions for blood and urine tests. If the pilot study indicates that indapamide could reduce these factors in blood, this would inform a much larger study using both indapamide and a placebo to assess it's effects on heart function.
Summary of Results:
This study was designed to test whether an antihypertensive medication (indapamide) could be useful to reduce the levels of FGF23 (a fibroblast growth factor related to severity and poor outcome of heart failure). Indapamide is known to act as a weak diuretic that could act to increase phosphate loss in the urine.
The study recruited a total of 20 patients. The planned recruitment was 110, but the study under-recruited due to a number of reasons: 1) patients were reluctant to participate as they were already on significant numbers of medications and adding another trial medication was viewed as too onerous. 2) the Covid pandemic led to cessation of recruitment to studies.
The plasma samples were assayed for brain natriuretic peptide (BNP) and FGF23. Overall, the indapamide lowered the BNP and FGF23 levels, although this fall in level was not statistically significant (due to the small number of subjects and the relatively low level of the biomarkers). Two patients with very high levels of FGF23 showed large falls in the values of FGF23, but as the majority of patients had low values which remained low on therapy, the change in FGF23 levels was not significant.
One patient developed a worsening of renal function possibly due to the weak diuretic effect of indapamide, but recovered with therapy withdrawal in hospital.
Further studies on using indapamide in heart failure should focus on using low doses in order not to precipitate a worsening of renal function, and should also examine therapies in patients who are known to have high FGF23 levels
East Midlands - Nottingham 1 Research Ethics Committee
Date of REC Opinion
28 Dec 2016