Kidney Week

Abstract: FR-PO1064

Results of a Randomized Multicentre Pilot Study of Sacubitril/Valsartan versus Irbesartan in Patients with CKD: United Kingdom Heart and Renal Protection (UK HARP)-III Trial

Session Information

• Late-Breaking Clinical Trial Posters
  November 03, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Chronic Kidney Disease (Non-Dialysis)

• 305 CKD: Clinical Trials and Tubulointerstitial Disorders

Authors

• Haynes, Richard, University of Oxford, Oxford, United Kingdom

Richard Haynes,

• Judge, Parminder K., University of Oxford, Oxford, United Kingdom

Parminder K. Judge,

• Staplin, Natalie, Clinical Trial Service Unit, University of Oxford, Oxford, United Kingdom

Natalie Staplin,

• Landray, Martin J., University of Oxford, Oxford, United Kingdom

Martin J. Landray,

• Baigent, Colin, University of Oxford, Oxford, United Kingdom

Colin Baigent,

Group or Team Name

• UK HARP-III Collaborative Group

Background

Angiotensin Receptor Neprilysin Inhibitor (ARNI) therapy inhibits the renin-angiotensin system (RAS) and increases concentrations of natriuretic and other vasoactive peptides. ARNI therapy may delay progression of kidney disease and prevent cardiovascular events. Trials among patients with heart failure have shown that treatment with ARNI significantly reduces the risk of cardiovascular events. However, the potential benefits in patients with CKD have not been studied. UK HARP-III is a randomized trial comparing the effects on kidney function, safety and tolerability of the ARNI sacubitril/valsartan (S/V) versus irbesartan (IRB) in patients with CKD.

Methods

Patients ≥18 years of age with either (i) an estimated glomerular filtration rate (eGFR) of ≥45 <60 mL/min/1.73m² and urine albumin:creatinine ratio (uACR) >20 mg/mmol; or (ii) eGFR ≥20 <45 mL/min/1.73 m² (regardless of uACR) were eligible to participate. After 4-7 week placebo run-in (including washout of RAS inhibitors), participants were randomly assigned S/V 97/103 mg twice daily or IRB 300 mg once daily. The primary outcome was measured glomerular filtration rate (mGFR) at 12 months. Other outcomes include effects on uACR, change in eGFR over time and the short-term safety and tolerability of S/V.

Results

414 participants were randomized. Mean eGFR was 35.4 ml/min/1.73m² and median uACR was 54 mg/mmol. Allocation to S/V had no effect on mGFR at 12 months (difference -0.1 [SE 0.7] ml/min/1.73m²) nor eGFR at any time point. Allocation to S/V led to a non-significant 9% (95% CI -1 to 18) reduction in uACR. S/V was well-tolerated and was not associated with excess of any serious adverse events. Allocation to S/V reduced study average systolic and diastolic blood pressure by 5.4 (3.4-7.4) and 2.1 (1.0-3.3) mmHg respectively. There was a non-significant excess of hyperkalaemia (>5.5 mmol/l) among those allocated S/V vs IRB (32% vs 24%; p=0.10).

Conclusion

Compared to irbesartan, S/V had no measurable effect on GFR or uACR. S/V was well-tolerated and no major hazards were observed. A large randomized trial is required to assess the effects of S/V on cardiovascular and renal outcomes.

Funding

• Commercial Support –