Effect of Short Term Aliskiren Treatment in Kidney Transplant Patients

• Sponsor: Brigham and Women's Hospital (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01437943
• Collaborator: Novartis (Industry)
• Enrollment: 10
• Location: 1
• Arms: 2
• Duration (Months): 21
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Kidney Disease; Kidney Failure, Chronic	Drug: Aliskiren; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: P-MR Spectroscopy Evaluation of the Effect of Short-Term Treatment With Aliskiren on Kidney β-ATP/Pi Level in Kidney Transplant Patients
• Study Start Date: Apr 1, 2010
• Actual Primary Completion Date: Jan 1, 2012
• Actual Study Completion Date: Jan 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Aliskiren Aliskiren 150 mg daily for 180 days	Drug: Aliskiren; Take 1 tablet (150 mg) by mouth daily for 180 days; Other Names: Tekturna
Placebo Comparator: Placebo Placebo identical to Aliskiren drug daily for 180 days	Drug: Placebo; Take 1 tablet (0 mg) daily for 180 days.

Outcome Measures

Primary Outcome Measures

1. Effect of Aliskiren on Kidney Metabolism [180 days (completion of treatment)]

   Evaluation of aliskiren on kidney metabolism by P-MR spectroscopy

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts 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.

Exclusion criteria include MR contraindications:

• electrical implants such as cardiac pacemakers or perfusion pumps

• ferromagnetic implants such as aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the eye, or steel implants

• ferromagnetic objects such as jewelry or metal clips in clothing

• pregnant volunteers

• pre-existing medical conditions including a likelihood of developing seizures or claustrophobic reactions

• any greater than normal potential for cardiac arrest

• subjects less than 18 years of age.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• Brigham and Women's Hospital
• Novartis

Investigators

• Principal Investigator: Anil Chandraker, MD, Brigham and Women's Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Anil K. Chandraker, MD, Medical Director of Renal Transplantation, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT01437943
• Other Study ID Numbers: 2010P000005
• First Posted: Sep 21, 2011
• Last Update Posted: May 1, 2017
• Last Verified: Mar 1, 2017

• Keywords provided by Anil K. Chandraker, MD, Medical Director of Renal Transplantation, Brigham and Women's Hospital: Transplant; Failure; Kidney
• Additional relevant MeSH terms: Kidney Diseases; Renal Insufficiency; Kidney Failure, Chronic

Study Results

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.

Arm/Group Title	Aliskiren	Placebo
Arm/Group Description	Aliskiren 150 mg daily for 180 days Aliskiren: Take 1 tablet (150 mg) by mouth daily for 180 days	Placebo daily for 180 days Placebo: Take 1 tablet by mouth daily for 180 days
Period Title: Overall Study
STARTED	7	3
COMPLETED	0	1
NOT COMPLETED	7	2

Baseline Characteristics

Arm/Group Title	Aliskiren	Placebo	Total
Arm/Group Description	Aliskiren 150 mg daily for 180 days Aliskiren: Take 1 tablet (150 mg) by mouth daily for 180 days	Placebo daily for 180 days Placebo: Take 1 tablet (0 mg) daily for 180 days	Total of all reporting groups
Overall Participants	7	3	10
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	6 85.7%	3 100%	9 90%
>=65 years	1 14.3%	0 0%	1 10%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	56.6	48	54
Sex: Female, Male (Count of Participants)
Female	1 14.3%	1 33.3%	2 20%
Male	6 85.7%	2 66.7%	8 80%
Region of Enrollment (participants) [Number]
United States	7 100%	3 100%	10 100%

Outcome Measures

1. Primary Outcome

Title	Effect of Aliskiren on Kidney Metabolism
Description	Evaluation of aliskiren on kidney metabolism by P-MR spectroscopy
Time Frame	180 days (completion of treatment)

Outcome Measure Data

Analysis Population Description

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/Group Title	Aliskiren	Placebo
Arm/Group Description	Aliskiren 150 mg daily for 180 days Aliskiren: Take 1 tablet (150 mg) by mouth daily for 180 days	Placebo identical to Aliskiren drug daily for 180 days Placebo: Take 1 tablet (0 mg) daily for 180 days.
Measure Participants	0	0
	0	0

Adverse Events

Time Frame	Adverse event data was collected continuously during subject participation starting at consent through month 6 or termination of the trial.
Arm/Group Title	Aliskiren		Placebo
Arm/Group Description	Aliskiren 150 mg daily for 180 days Aliskiren: Take 1 tablet (150 mg) by mouth daily for 180 days		Placebo daily for 180 days Placebo: Take 1 tablet by mouth daily for 180 days
All Cause Mortality
	Aliskiren		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Aliskiren		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/7 (28.6%)		1/3 (33.3%)
Blood and lymphatic system disorders
Left knee hemarthrosis and DVT	1/7 (14.3%)	1	0/3 (0%)	0
Gastrointestinal disorders
GI bleed	1/7 (14.3%)	2	0/3 (0%)	0
Infections and infestations
Salmonella group B	0/7 (0%)	0	1/3 (33.3%)	1
Other (Not Including Serious) Adverse Events
	Aliskiren		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/7 (71.4%)		1/3 (33.3%)
Cardiac disorders
Hypotension	0/7 (0%)		1/3 (33.3%)
Gastrointestinal disorders
Diarrhea	5/7 (71.4%)		1/3 (33.3%)
Abdominal Pain	1/7 (14.3%)		1/3 (33.3%)
Musculoskeletal and connective tissue disorders
Lower extremity weakness	1/7 (14.3%)		0/3 (0%)
Renal and urinary disorders
Urinary tract infection	0/7 (0%)		1/3 (33.3%)
Elevated creatinine	0/7 (0%)		1/3 (33.3%)

Limitations/Caveats

In December 2011, all studies involving Aliskiren were terminated by Novartis after interim analysis of the ALTITUDE trial.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.