Clinical trial NCT01235910: Clinical Pharmacology of Aliskiren in Combination With Cyclosporine in Cardiac Transplantation
Official title: Clinical Pharmacology of Aliskiren in Combination With Cyclosporine in Cardiac Transplantation
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Hypertension
Cardiac Transplantation
Keywords: Hypertension
Cardiac transplantation
Aliskiren
Cyclosporine
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: American Heart Association
First posted: 2010-11-07
Enrollment: 1
Sex: ALL
Minimum age (years): 21
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Dose-normalized Cyclosporine Area Under the Plasma Concentration-time Curve (AUC)
timeFrame: 7 days, 14 days, 30 days (End of Study)
Secondary outcomes:
measure: Aliskiren Plasma Concentrations
timeFrame: 2 weeks
measure: Blood Pressure
timeFrame: 2 weeks
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Christina L Aquilante, Pharm.D.
role: PRINCIPAL_INVESTIGATOR
References: