Kidney Disease, Kidney Failure, Chronic
Conditions
Keywords
Transplant, Failure, Kidney
Brief summary
The purpose of this study is to evaluate the effect of a short-term aliskiren treatment on kidney metabolism in patients at high risk for developing kidney dysfunction (i.e. kidney transplanted patients). The study is aimed at evaluating if any effect on kidney metabolism \[using proton MR Spectroscopy(1H-MRS)\] can be detected following a 6 months treatment with aliskiren regardless of its anti-hypertensive role. 1H-MRS can record a larger number of chemical species (up to 40) in the kidney, and monitor changes according to the pathologic state and health of the transplanted kidney.
Interventions
DRUGAliskiren
Take 1 tablet (150 mg) by mouth daily for 180 days
DRUGPlacebo
Take 1 tablet (0 mg) daily for 180 days.
Sponsors
Novartis
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Stable patients with end stage renal disease receiving cadaveric kidney transplantation will be enrolled. Patients must have at least 6 months of follow-up to be included in the study. Patients must have stable creatinine levels in the last 6 months (no change\>0.5 mg/dl). * Patients with a systolic blood pressure of 120 or above
Exclusion criteria
* Serum potassium \> 5.0 mmol/L (at the visit directly preceding Randomization); * History of any cardiovascular event (stroke, TIA, MI, unstable angina, CABG, percutaneous coronary intervention, hospitalization due to HF) during the 3 months prior to Visit 1. If a patient experiences such an event between Visit 1 and randomization at Visit 3, he/she should be withdrawn from the screening phase. If suitable, the patient can be re-screened at a later stage; * Hypertension (at enrollment): any patient with msSBP ≥ 170 mmHg or msDBP ≥ 110 mmHg; * Congestive heart failure NYHA class III and IV; * Concomitant treatment with two (2) or more renin-angiotensin-aldosterone system blocking agents, e.g. ACEI, ARB or aldosterone-antagonist; * Unstable serum creatinine, no patients with creatinine \>2.5 mg/dl will be enrolled; * Second (II) or third (III) degree heart block without a pacemaker; * Concurrent potentially life threatening arrhythmia or other uncontrolled arrhythmia; * Clinically significant valvular heart disease; * Known renal artery stenosis; * Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of the study drugs including, but not limited to, any of the following: (i) History of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection (patients with previous bariatric surgery \> 6 months prior to Visit 1 are allowed to participate); (ii) Any history of pancreatic injury, pancreatitis or evidence of impaired pancreatic function/injury as indicated by abnormal lipase or amylase; (iii) Evidence of hepatic disease as determined by any one of the following: SGPT value exceeding 3 x Upper Limit of Normal (ULN) at Visit 1, a history of hepatic encephalopathy, a history of cirrhosis, esophageal varices, or a history of portocaval shunt. * History of malignancy other than basal cell skin cancer within the past five years. * Any concurrent life threatening condition with a life expectancy less than 2 years. * History or evidence of drug or alcohol abuse within the last 12 months. * Any surgical or medical condition, which in the opinion of the investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study. * History of hypersensitivity to any of the study drugs or to medications belonging to the same therapeutic class as the study drugs as well as known or suspected contraindications to the study drugs. * History of noncompliance to medical regimens or unwillingness to comply with the study protocol. * Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer * Any condition that in the opinion of the investigator would jeopardize the evaluation of efficacy or safety. * Persons directly involved in the execution of this protocol. * Pregnant or nursing (lactating) women * Women of Child-Bearing Potential (WOCBP) unless postmenopausal for at least one year, surgically sterile or using effective methods of contraception as defined by local Health Authorities. * Treatment with Cyclosporine.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effect of Aliskiren on Kidney Metabolism | 180 days (completion of treatment) | Evaluation of aliskiren on kidney metabolism by P-MR spectroscopy |
Countries
United States
Participant flow
Recruitment details
10 subjects were recruited into the trial however none completed the treatment/follow-up as Novartis terminated all studies involving Aliskiren.
Participants by arm
| Arm | Count |
|---|---|
| Aliskiren Aliskiren 150 mg daily for 180 days
Aliskiren: Take 1 tablet (150 mg) by mouth daily for 180 days | 7 |
| Placebo Placebo daily for 180 days
Placebo: Take 1 tablet (0 mg) daily for 180 days | 3 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Aliskiren trials terminated by Novartis | 4 | 2 |
| Overall Study | Subject expressed pregnancy plans | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Aliskiren | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 6 Participants | 9 Participants |
| Age, Continuous | 48 years | 56.6 years | 54 years |
| Region of Enrollment United States | 3 participants | 7 participants | 10 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 2 Participants | 6 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 7 | 1 / 3 |
| serious Total, serious adverse events | 2 / 7 | 1 / 3 |
Outcome results
Primary
Effect of Aliskiren on Kidney Metabolism
Evaluation of aliskiren on kidney metabolism by P-MR spectroscopy
Time frame: 180 days (completion of treatment)
Population: Only one subject completed study drug and no subjects had completed the 6 month P-MR scan at the time the trial was terminated. Because of this, we were not able to analyze the primary outcome.
| Arm | Measure | Value |
|---|---|---|
| Aliskiren | Effect of Aliskiren on Kidney Metabolism | 0 |
| Placebo | Effect of Aliskiren on Kidney Metabolism | 0 |