Cardiac Transplantation, Hypertension
Conditions
Keywords
Hypertension, Cardiac transplantation, Aliskiren, Cyclosporine
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.
Interventions
DRUGAliskiren
Aliskiren 75 mg once daily x 2 weeks, then aliskiren 150 mg once daily x 2 weeks, if blood pressure allows
Sponsors
American Heart Association
University of Colorado, Denver
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 70 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aliskiren Aliskiren 75 mg once daily x 2 weeks, then aliskiren 150 mg once daily x 2 weeks, if blood pressure allows
Aliskiren: Aliskiren 75 mg once daily x 2 weeks, then aliskiren 150 mg once daily x 2 weeks, if blood pressure allows | 1 |
| Total | 1 |
Baseline characteristics
| Characteristic | Aliskiren |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Age, Continuous | 58 years STANDARD_DEVIATION 0 |
| Region of Enrollment United States | 1 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 1 |
| serious Total, serious adverse events | 0 / 1 |
Outcome results
Primary
Dose-normalized Cyclosporine Area Under the Plasma Concentration-time Curve (AUC)
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.
Time frame: 7 days, 14 days, 30 days (End of Study)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aliskiren | Dose-normalized Cyclosporine Area Under the Plasma Concentration-time Curve (AUC) | NA ng*h/ml/mg |
Secondary
Aliskiren Plasma Concentrations
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.
Time frame: 2 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aliskiren | Aliskiren Plasma Concentrations | NA ng*h/ml/mg |
Secondary
Blood Pressure
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.
Time frame: 2 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aliskiren | Blood Pressure | NA mmHg |