Clinical Pharmacology of Aliskiren in Combination With Cyclosporine in Cardiac Transplantation

Phase 4

Terminated

• Conditions: Hypertension; Cardiac Transplantation
• Interventions: Drug: Aliskiren

• Registration Number: NCT01235910
• Lead Sponsor: University of Colorado, Denver

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of the blood pressure medication, aliskiren, in heart transplant patients. In terms of safety, the investigators will evaluate the blood levels of aliskiren and determine if aliskiren alters the blood levels of the anti-rejection medication, cyclosporine, in these patients. In terms of efficacy, the investigators will determine how well aliskiren lowers blood pressure in heart transplant patients.

Detailed Description

Hypertension is a major complication following cardiac transplantation, with a prevalence of 93% at 5 years post-transplant. Post-cardiac transplant hypertension is due to multiple factors such as use of cyclosporine, chronic kidney disease, and denervation. Hypertension in this population is difficult to treat, and most patients require therapy with multiple antihypertensive agents in order to achieve adequate blood pressure control. Aliskiren, a direct renin inhibitor, is a novel antihypertensive agent with a unique mechanism of action and potent blood pressure-lowering effects. As such, aliskiren is an attractive treatment option for post-cardiac transplant hypertension. This study will characterize the pharmacokinetic drug-drug interaction profile, pharmacodynamics, and safety of aliskiren 75 mg daily (low-dose) and 150 mg daily, when given in combination with cyclosporine, in cardiac transplant patients.

Study Timeline

• Study First Submitted: 2010-11-03
• Study First Submitted QC: 2010-11-04
• Study First Posted: 2010-11-07
• Study Start: 2011-05
• Primary Completion: 2012-12
• Study Completion: 2012-12
• Results First Submitted: 2014-12-10
• Results First Submitted QC: 2015-07-21
• Results First Posted: 2015-08-18
• Status Verified: 2018-05
• Last Update Submitted: 2018-05-30
• Last Update Posted: 2018-06-29

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 1

Inclusion Criteria

• 6 months or more since cardiac transplant
• Clinically stable from a transplant perspective
• Maintained on a stable immunosuppressant regimen containing cyclosporine + an antiproliferative agent (e.g., azathioprine, mycophenolate), +/- an oral steroid
• Hypertension, as defined by a seated average systolic blood pressure of ≥ 140 mm Hg and a seated average diastolic blood pressure of ≥ 90 mm Hg, based on 3 separate measurements, spaced 2 minutes apart.

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Exclusion Criteria

• Clinical instability from a cardiac transplant perspective
• Contraindications to aliskiren therapy
• Conditions that may increase the risk of aliskiren adverse effects
• Severe hypertension
• Concomitant medications known to increase or decrease aliskiren plasma exposure.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1	Aliskiren	Aliskiren 75 mg once daily x 2 weeks, then aliskiren 150 mg once daily x 2 weeks, if blood pressure allows

Primary Outcome Measures

Name	Time	Method
Dose-normalized Cyclosporine Area Under the Plasma Concentration-time Curve (AUC)	7 days, 14 days, 30 days (End of Study)	The study was stopped due to difficulty finding patients who met the strict inclusion criteria. Only one patient was started on the study drug. as a result we did not analyze any cyclosporine PK (e.g.(AUCs) for this study.

Secondary Outcome Measures

Name	Time	Method
Aliskiren Plasma Concentrations	2 weeks	Maximum plasma concentration; area under the concentration-time curve, half-life, oral clearance; The study was stopped due to difficulty finding patients who met the strict inclusion criteria. Only one patient was started on the study drug. as a result we did not analyze any PK (e.g.(AUCs) for this study.
Blood Pressure	2 weeks	The study was stopped due to difficulty finding patients who met the strict inclusion criteria. Only one patient was started on the study drug. as a result we did not analyze any blood pressure for this study.

Trial Locations

Locations (1)

University of Colorado Denver; 🇺🇸 Aurora, Colorado, United States