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To Study the Effects of Aliskiren on Albuminuria and Various Biomarkers in Patients With Nephropathy (ARIA)

This study has been terminated.
(In consequence of termination of ALTITUDE. A number of studies were continued in consultation with the Altitude Data Monitoring Committee.)
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01302899
First received: February 9, 2011
Last updated: December 21, 2012
Last verified: December 2012
  Purpose

The study is designed to primarily assess the effect of aliskiren on albuminuria in patients with non-diabetic nephropathy when treated with ramipril and volume intervention.


Condition Intervention Phase
Non-diabetic Nephropathy
Drug: Aliskiren
Drug: Placebo to Aliskiren
Drug: Hydrochlorothiazide (HCTZ)
Drug: Placebo to Hydrochlorothiazide (HCTZ)
Drug: Ramipril
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: A Single-blind, Double Dummy, Randomized, Multi-dose, Two Sequence, Crossover, Study to Investigate the Effects of Renin Inhibitor (Aliskiren 300 mg) on Albuminuria in Non-diabetic Nephropathy Patients Treated With Ramipril 10 mg and Volume Intervention (ARIA)

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Effect of Aliskiren on Albuminuria as Measured by Urinary Albumin Excretion Rate (UAER) [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
    Two 24-hour collections of urine were to be made at each study visit. The arithmetic mean of the two collections were planned to be used in the calculation of summary statistics and the statistical analyses.

  • Effect of Aliskiren on Albuminuria as Measured by Creatinine Indexed Albumin [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
    Two 24-hour collections of urine were to be made at each study visit. The arithmetic mean of the two collections were planned to be used in the calculation of summary statistics and the statistical analyses.


Secondary Outcome Measures:
  • Mean Sitting Systolic Blood Pressure (msSBP) [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
    At study entry, blood pressure (BP) was measured in both arms. If there was a clinically relevant difference in readings between arms (≥ 10 mmHg in systolic BP and/or ≥ 5 mmHg in diastolic BP), the arm with higher BP reading was used. If there was no clinically significant difference between arms, the non-dominant arm was used through out study. Systolic blood pressure were assessed after the patient rested quietly in the sitting position for at least 3 minutes. For each sitting assessment, blood pressure was assessed at least 3 times. From these assessments, msSBP was calculated. All BP measurements were to be performed on the same arm.

  • Mean Sitting Diastolic Blood Pressure (msDBP) [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
    At study entry, blood pressure (BP) was measured in both arms. If there was a clinically relevant difference in readings between arms (≥ 10 mmHg in systolic BP and/or ≥ 5 mmHg in diastolic BP), the arm with higher BP reading was used. If there was no clinically significant difference between arms, the non-dominant arm was used through out study. Diastolic blood pressure were assessed after the patient rested quietly in the sitting position for at least 3 minutes. For each sitting assessment, blood pressure was assessed at least 3 times. From these assessments, msDBP was calculated. All BP measurements were to be performed on the same arm.

  • Mean Glomerular Filtration Rate (GFR) as Measurement of Renal Function [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
    All patients had to visit the main center for renal function measurements. The measurements were performed using the constant infusion method with I-iothalamate (IOT) and I-hippuran. GFR was calculated as the urinary clearance of IOT.

  • Mean Effective Renal Plasma Flow (ERPF) as One of Hemodynamic Assessments [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
  • Percentage of Renal Filtration Fraction (RFF) as One of Hemodynamic Assessments [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
  • Mean Extracellular Volume (ECV) as One of Hemodynamic Assessments [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
  • Plasma Rennin Activity (PRA) [ Time Frame: Baseline to week 26 ] [ Designated as safety issue: No ]
    Blood biomarkers were obtained from blood samples in all patients at the time points such as baseline, week 6, week 12, week 18 and week 26. Plasma PRA is a direct measure of the formation of Ang I in the plasma.

  • Plasma Rennin Concentration (PRC) [ Time Frame: Baseline to week 26 ] [ Designated as safety issue: No ]
    Blood biomarkers were obtained from blood samples in all patients at the time points such as baseline, week 6, week 12, week 18 and week 26. PRC measures the concentration of immunoactive renin in the plasma.

  • Number of Participants With Adverse Events, Serious Adverse Events and Death as Assessment of Safety and Tolerability of Aliskiren Added to Ramipril [ Time Frame: 26 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 8
Study Start Date: January 2011
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ramipril (Ram) +HCTZ/Ram+Aliskiren (Ali)+HCTZ/Ram+Ali/Ram

Period 1(Day 1 to end of week 6): 1 tablet ramipril 10 mg once daily (o.d.) + 2 tablets placebo to aliskiren 150mg o.d. + 1 capsule Hydrochlorothiazide (HCTZ) 25 mg o.d.

Period 2 (Weeks 7 to 12): 1 tablet ramipril 10 mg o.d.+ 1 tablet aliskiren 150 mg in 1st week of period; thereafter, 2 tablets aliskiren 150mg o.d.+ 1 capsule HCTZ 25 mg o.d.

Period 3 (Weeks 13 to 18): 1 tablet ramipril 10 mg o.d. + 2 tablets aliskiren 150mg o.d. + 1 capsule placebo to HCTZ 25 mg o.d.

Period 4 (Weeks 19 to 26): 1 tablet ramipril 10 mg o.d. + 2 tablets placebo to aliskiren 150mg o.d. + 1 capsule placebo to HCTZ 25 mg o.d.

Drug: Aliskiren
Aliskiren 150 mg (Tablet)
Drug: Placebo to Aliskiren
Aliskiren 150 mg Matching Placebo (Tablet)
Drug: Hydrochlorothiazide (HCTZ)
HCTZ 25mg (Capsule)
Drug: Placebo to Hydrochlorothiazide (HCTZ)
HCTZ 25mg (Capsule) Matching Placebo
Drug: Ramipril
Ramipril 10mg (Tablet)
Experimental: Ramipril (Ram) +HCTZ/Ram+Aliskiren (Ali)/Ram+Ali + HCTZ/Ram

Period 1(Day 1 to end of week 6): 1 tablet ramipril 10 mg once daily (o.d.) + 2 tablets placebo to aliskiren 150mg o.d. + 1 capsule Hydrochlorothiazide (HCTZ) 25 mg o.d.

Period 2 (Weeks 7 to 12): 1 tablet ramipril 10 mg o.d.+ 1 tablet aliskiren 150 mg in 1st week of period; thereafter, 2 tablets aliskiren 150mg o.d.+ 1 capsule placebo to HCTZ 25 mg o.d.

Period 3 (Weeks 13 to 18): 1 tablet ramipril 10 mg o.d. + 2 tablets aliskiren 150mg o.d. + 1 capsule HCTZ 25 mg o.d.

Period 4 (Weeks 19 to 26): 1 tablet ramipril 10 mg o.d. + 2 tablets placebo to aliskiren 150mg o.d. + 1 capsule placebo to HCTZ 25 mg o.d.

Drug: Aliskiren
Aliskiren 150 mg (Tablet)
Drug: Placebo to Aliskiren
Aliskiren 150 mg Matching Placebo (Tablet)
Drug: Hydrochlorothiazide (HCTZ)
HCTZ 25mg (Capsule)
Drug: Placebo to Hydrochlorothiazide (HCTZ)
HCTZ 25mg (Capsule) Matching Placebo
Drug: Ramipril
Ramipril 10mg (Tablet)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female subjects, age 18 years and above
  • Patients with chronic kidney disease of non-diabetic origin
  • Glomerular filtration rate >30 ml/min/1.73m2
  • Patients with a history of hypertension and msSBP (mean systolic blood pressure) of <160 mm Hg and msDBP (mean diastolic blood pressure) <105 mm Hg at screening and baseline.
  • Subjects must have a body mass index (BMI) within the range of 18 and 35 kg/m2

Exclusion Criteria:

  • Previously treated (within 3 months of screening) with aliskiren or a combination of aliskiren and ramipril.
  • Severe hypertension (msDBP ≥110 mmHg and msSBP ≥180 mmHg)
  • Pregnant or nursing (lactating) women,
  • A medical history of unstable coronary artery disease, myocardial infarction, coronary bypass surgery or cerebrovascular accident within the last six (6) months
  • Diabetes mellitus, Heart failure
  • High rate of renal function loss
  • History of severe hypersensitivity or contraindications to any of the medications or drugs belonging to the similar therapeutic class as the study drugs and the excipients.
  • History of liver disease, positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result
  • History of immunodeficiency diseases, including a positive HIV (ELISA and Western blot) test result.

Other protocol-defined inclusion/exclusion criteria applied

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01302899

Locations
Netherlands
Novartis Investigative Site
Groningen, Netherlands
Novartis Investigative Site
Leeuwarden, Netherlands
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01302899     History of Changes
Other Study ID Numbers: CSPP100A2260, 2009-012196-10
Study First Received: February 9, 2011
Results First Received: December 21, 2012
Last Updated: December 21, 2012
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Additional relevant MeSH terms:
Albuminuria
Kidney Diseases
Proteinuria
Signs and Symptoms
Urination Disorders
Urologic Diseases
Urological Manifestations
Hydrochlorothiazide
Ramipril
Angiotensin-Converting Enzyme Inhibitors
Antihypertensive Agents
Cardiovascular Agents
Diuretics
Enzyme Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Natriuretic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protease Inhibitors
Sodium Chloride Symporter Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014