Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints (Core and Extension Phases)

Summary

The purpose of this study was to determine whether, in patients with type 2 diabetes and pre-existing disease of the heart and the circulatory system and/or the kidney, aliskiren at a target dose of 300 mg once daily (compared to placebo), on top of conventional treatment, reduces death and disease caused by the heart, the circulatory system and the kidney. AMENDMENT 4 RATIONALE (MARCH 2012) : Protocol amendment 4 served to address the data monitoring committee recommendation dated 14 Dec 2011 to discontinue study treatment in all participating patients. It also addressed the subsequent Health Authorities request to implement a 12 month safety follow-up period (actual duration was 9 months in average) post study drug discontinuation.

Timeline

Start

2007-10

Primary completion

2013-02

Completion

2013-02

Publications

• Jongs N, Gasparyan SB, Frison L, Schloemer P, Brinker M, Little DJ, Heerspink HJL. Use of eGFR Slope Thresholds as End Point Components in a Kidney Disease Progression Hierarchical Composite End Point. J Am Soc Nephrol. 2025 Dec 1;36(12):2421-2430. doi: 10.1681/ASN.0000000766. Epub 2025 Jun 17.
• Heerspink HJL, Jongs N, Schloemer P, Little DJ, Brinker M, Tasto C, Karpefors M, Wheeler DC, Bakris G, Perkovic V, Nkulikiyinka R, Rossert J, Gasparyan SB. Development and Validation of a New Hierarchical Composite End Point for Clinical Trials of Kidney Disease Progression. J Am Soc Nephrol. 2023 Dec 1;34(12):2025-2038. doi: 10.1681/ASN.0000000000000243. Epub 2023 Oct 24.
• Malachias MVB, Jhund PS, Claggett BL, Wijkman MO, Bentley-Lewis R, Chaturvedi N, Desai AS, Haffner SM, Parving HH, Prescott MF, Solomon SD, De Zeeuw D, McMurray JJV, Pfeffer MA. NT-proBNP by Itself Predicts Death and Cardiovascular Events in High-Risk Patients With Type 2 Diabetes Mellitus. J Am Heart Assoc. 2020 Oct 20;9(19):e017462. doi: 10.1161/JAHA.120.017462. Epub 2020 Sep 23.
• Heerspink HJ, Persson F, Brenner BM, Chaturvedi N, Brunel P, McMurray JJ, Desai AS, Solomon SD, Pfeffer MA, Parving HH, de Zeeuw D. Renal outcomes with aliskiren in patients with type 2 diabetes: a prespecified secondary analysis of the ALTITUDE randomised controlled trial. Lancet Diabetes Endocrinol. 2016 Apr;4(4):309-17. doi: 10.1016/S2213-8587(15)00469-6. Epub 2016 Jan 14.
• Parving HH, Brenner BM, McMurray JJ, de Zeeuw D, Haffner SM, Solomon SD, Chaturvedi N, Persson F, Desai AS, Nicolaides M, Richard A, Xiang Z, Brunel P, Pfeffer MA; ALTITUDE Investigators. Cardiorenal end points in a trial of aliskiren for type 2 diabetes. N Engl J Med. 2012 Dec 6;367(23):2204-13. doi: 10.1056/NEJMoa1208799. Epub 2012 Nov 3.
• Lambers Heerspink HJ, Perkovic V, de Zeeuw D. Renal and cardio-protective effects of direct renin inhibition: a systematic literature review. J Hypertens. 2009 Dec;27(12):2321-31. doi: 10.1097/HJH.0b013e3283310f92.

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Indications