Ramipril versus placebo in kidney transplant patients with proteinuria: A multicentre, double-blind, randomised controlled trial.
Knoll GA, Fergusson D, et al.The Lancet Diabetes and Endocrinology 2016; 4(4): 318-326.
Aims
To compare the clinical outcomes of ramipril versus placebo in kidney transplant recipients with proteinuria.
Interventions
Participants that tolerated a 2-week open-label trial of oral ramipril (5 mg daily) were randomised to receive either ramipril or placebo capsule for up to 4 years (oral 5 mg daily for 2 weeks and then 5 mg oral twice daily thereafter).
Participants
213 kidney transplant recipients who were ≥ 6 months posttransplant with an eGFR between 20 mL/min/1·73m² and 55 mL/min/1·73m² and proteinuria 0·2 g per day or greater (enrolled prior February 25, 2008) and ≥ 3 months posttransplant with an eGFR 20 mL/min/1·73m² or greater after this date
Outcomes
The primary outcome measured was a composite of a doubling of serum creatinine, end-stage renal disease, or death. Secondary measured outcomes included the change in measured GFR, quality of life, proteinuria, blood pressure, cardiovascular events, admissions to hospital, hyperkalaemia, and haemoglobin concentration.
Follow-up
Every 6 months for a maximum of 48 months (4 years)
CET Conclusions
This was a well-designed and conducted, blinded RCT that was halted early due to resource constraints. The authors also reported the increased use of ACE inhibitors and ARBs in the transplant population during the study period, which hampered recruitment. At the final inclusion point Ramipril 5mg did not lead to a significant reduction in the composite outcome: doubling of serum creatinine, end-stage renal disease, or death. The authors have attempted to extrapolate the results to the target sample size, concluding that there is unlikely to be a benefit of Ramipril, and if there is any benefit it will be small. The Ramipril group had a significantly higher number of adverse events and discontinuations than the placebo group, and lower Hb at the end of the trial. There was no difference in cardiovascular events or GFR. Blood pressure control was very good in both groups, but slightly (and significantly) better in the Ramipril group.
Data analysis
Available case analysis
Trial registration
ISRCTN - 78129473