Clinical Pharmacology of Aliskiren in Combination With Cyclosporine in Cardiac Transplantation

This study has been terminated.
(Study was stopped early due to difficulty finding patients who met I/E criteria.)
American Heart Association
Information provided by (Responsible Party):
University of Colorado, Denver Identifier:
First received: November 3, 2010
Last updated: July 21, 2015
Last verified: July 2015
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.

Condition Intervention Phase
Cardiac Transplantation
Drug: Aliskiren
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Clinical Pharmacology of Aliskiren in Combination With Cyclosporine in Cardiac Transplantation

Resource links provided by NLM:

Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:
  • Dose-normalized Cyclosporine Area Under the Plasma Concentration-time Curve (AUC) [ Time Frame: 7 days, 14 days, 30 days (End of Study) ] [ Designated as safety issue: Yes ]
    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:
  • Aliskiren Plasma Concentrations [ Time Frame: 2 weeks ] [ Designated as safety issue: Yes ]
    Maximum plasma concentration; area under the concentration-time curve, half-life, oral clearance

  • Blood Pressure [ Time Frame: 2 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 1
Study Start Date: May 2011
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Aliskiren 75 mg once daily x 2 weeks, then aliskiren 150 mg once daily x 2 weeks, if blood pressure allows
Drug: Aliskiren
Aliskiren 75 mg once daily x 2 weeks, then aliskiren 150 mg once daily x 2 weeks, if blood pressure allows
Other Names:
  • Tekturna (aliskiren)
  • Neoral (cycolosporine)

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. Our 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.

Ages Eligible for Study:   21 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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.

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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Please refer to this study by its identifier: NCT01235910

United States, Colorado
University of Colorado Denver
Aurora, Colorado, United States, 80045
Sponsors and Collaborators
University of Colorado, Denver
American Heart Association
Principal Investigator: Christina L Aquilante, Pharm.D. University of Colorado, Denver
  More Information

No publications provided

Responsible Party: University of Colorado, Denver Identifier: NCT01235910     History of Changes
Other Study ID Numbers: 10-0746
Study First Received: November 3, 2010
Results First Received: December 10, 2014
Last Updated: July 21, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Colorado, Denver:
Cardiac transplantation

Additional relevant MeSH terms:
Anti-Infective Agents
Antifungal Agents
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses processed this record on November 27, 2015