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Trial record 1 of 1 for:    CSPP100E2337
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Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints (Core and Extension Phases) (ALTITUDE)

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ClinicalTrials.gov Identifier: NCT00549757
Recruitment Status : Terminated (Lack of benefit and safety concern)
First Posted : October 26, 2007
Results First Posted : March 18, 2014
Last Update Posted : April 21, 2014
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE October 24, 2007
First Posted Date  ICMJE October 26, 2007
Results First Submitted Date  ICMJE February 3, 2014
Results First Posted Date  ICMJE March 18, 2014
Last Update Posted Date April 21, 2014
Study Start Date  ICMJE October 2007
Actual Primary Completion Date February 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 1, 2014)
  • Percentage of Participants With Occurrence of Primary Composite Endpoint (Core : Active Treatment Phase) [ Time Frame: Time from randomization to the first event (Maximum 50 months) ]
    Occurrence was defined as the first event of the following composite primary endpoint:
    • Cardiovascular (CV) death
    • Resuscitated sudden death
    • Non-fatal myocardial infarction (MI)
    • Non-fatal stroke
    • Unplanned hospitalization for heart failure (HF)
    • Onset of end-stage renal disease (ESRD) or death due to renal failure. Onset of ESRD was defined as initiation of dialysis, renal transplantation, or a serum creatinine concentration above 6.0 mg/dL (530 μmol/L), sustained for at least a month.
    • Doubling of baseline serum creatinine concentration, sustained for at least one month. To fulfill the endpoint, the serum creatinine concentration had to be above the upper limit of normal for men and women according to the central laboratory. The upper limit of normal for men is 1.20 mg/dL and for women is 0.91 mg/dL.
  • Percentage of Participants With Cardiovascular (CV) Death (Core: Active Treatment Phase) [ Time Frame: Time from randomization to the first event (Maximum 50 months) ]
  • Percentage of Participants With Resuscitated Sudden Death (Core: Active Treatment Phase) [ Time Frame: Time from randomization to the first event (Maximum 50 Months) ]
    Resuscitated sudden death was adjudicated when a subject experiences sudden death or cardiac arrest and is successfully resuscitated by cardioversion, defibrillation or cardiopulmonary resuscitation with a meaningful recovery of consciousness. This definition excludes known transient losses of consciousness such as seizure or vasovagal episodes that do not reflect significant cardiac dysfunction.
  • Percentage of Participants With Fatal/Non-fatal Myocardial Infarction (MI) (Core: Active Treatment Phase) [ Time Frame: Time from randomization to the first event (Maximum 50 Months) ]
  • Percentage of Participants With Fatal/Non-fatal Stroke (Core: Active Treatment Phase) [ Time Frame: Time from randomization to the first event (Maximum 50 Months) ]
  • Percentage of Participants With Onset of End-stage Renal Disease (ESRD) (Core: Active Treatment Phase) [ Time Frame: Time from randomization to the first event (Maximum 50 Months) ]
    ESRD is defined as initiation of dialysis, renal transplantation, or a serum creatinine concentration above 6.0 mg/dL (530 µmol per liter) or renal death
  • Percentage of Participants With Doubling of Baseline Serum Creatinine Concentration, Sustained for at Least One Month (Core: Active Treatment Phase) [ Time Frame: Time from randomization to the first event (Maximum 50 Months) ]
    To fulfill the endpoint, the serum creatinine concentration had to be above the upper limit of normal for men and women according to the central laboratory. The upper limit of normal for men is 1.20 mg/dL and for women is 0.91 mg/dL.
  • Percentage of Participants With Unplanned Hospitalization for Heart Failure (Core: Active Treatment Phase) [ Time Frame: Time from randomization to the first event (Maximum 50 Months) ]
  • Percentage of Participants With All Cause Mortality (Core: Active Treatment Phase) [ Time Frame: Time from randomization to the first event (Maximum 50 months) ]
  • Percentage of Participants With Occurrence of Primary Composite Endpoint (Extension Phase) [ Time Frame: From cut-off date (20Dec2011/End of Treatment (EOT) ) to the first event after cut-off date (9 months in average) ]
    Occurrence was defined as the first event of the following composite primary endpoint:
    • Cardiovascular (CV) death
    • Resuscitated sudden death
    • Non-fatal myocardial infarction (MI)
    • Non-fatal stroke
    • Unplanned hospitalization for heart failure (HF)
    • Onset of end-stage renal disease (ESRD) or death due to renal failure. Onset of ESRD was defined as initiation of dialysis, renal transplantation, or a serum creatinine concentration above 6.0 mg/dL (530 μmol/L), sustained for at least a month.
    • Doubling of baseline serum creatinine concentration, sustained for at least one month. To fulfill the endpoint, the serum creatinine concentration had to be above the upper limit of normal for men and women according to the central laboratory. The upper limit of normal for men is 1.20 mg/dL and for women is 0.91 mg/dL.
  • Percentage of Participants With Cardiovascular (CV) Death (Extension Phase) [ Time Frame: from cut-off date (20Dec2011/End of Treatment (EOT) ) to the first event after cut-off date (9 months in average) ]
  • Percentage of Participants With Resuscitated Sudden Death (Extension Phase) [ Time Frame: From cut-off date (20Dec2011/End of Treatment (EOT) ) to the first event after cut-off date (9 months in average) ]
  • Percentage of Participants Fatal/Non-fatal Myocardial Infarction (MI) (Extension Phase) [ Time Frame: From cut-off date (20Dec2011/End of Treatment (EOT) ) to the first event after cut-off date (9 month in average) ]
  • Percentage of Participants With Fatal/Non-fatal Stroke (Extension Phase) [ Time Frame: From cut-off date (20Dec2011/End of Treatment (EOT) ) to the first event after cut-off date (9 months in average) ]
  • Percentage of Participants With Onset of End-stage Renal Disease (ESRD) (Extension Phase) [ Time Frame: From cut-off date (20Dec2011/End of Treatment (EOT) ) to the first event after cut-off date (9 months in average) ]
    ESRD is defined as initiation of dialysis, renal transplantation, or a serum creatinine concentration above 6.0 mg/dL (530 µmol per liter) or renal death
  • Percentage of Participants Doubling of Baseline Serum Creatinine Concentration, Sustained for at Least One Month (Extension Phase) [ Time Frame: From cut-off date (20Dec2011/End of Treatment (EOT) ) to the first event after cut-off date (9 months in average) ]
    To fulfill the endpoint, the serum creatinine concentration had to be above the upper limit of normal for men and women according to the central laboratory. The upper limit of normal for men is 1.20 mg/dL and for women is 0.91 mg/dL.
  • Percentage of Participants With Unplanned Hospitalization for Heart Failure (Extension Phase) [ Time Frame: From cut-off date (20Dec2011/End of Treatment (EOT) ) to the first event after cut-off date (9 months in average) ]
  • Percentage of Participants With All Cause Mortality (Extension Phase) [ Time Frame: from cut-off date (20Dec2011/End of Treatment (EOT) ) to the first event after cut-off date (9 months in average) ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 25, 2007)
  • Cardiovascular (CV) death [ Time Frame: Time from randomization to the first event of the following composite endpoint ]
  • Resuscitated sudden death [ Time Frame: Time from randomization to the first event of the following composite endpoint ]
  • Non-fatal myocardial infarction (MI) [ Time Frame: Time from randomization to the first event of the following composite endpoint ]
  • Non-fatal stroke [ Time Frame: Time from randomization to the first event of the following composite endpoint ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 3, 2014)
  • Percentage of Participants With Occurrence of Secondary Cardiovascular Composite Endpoint (Core: Active Treatment Phase) [ Time Frame: Time from randomization to the first event (Maximum 50 months) ]
    Occurrence was defined as the first event of the following secondary cardiovascular composite endpoint:
    • Cardiovascular (CV) death
    • Resuscitated sudden death
    • Non-fatal myocardial infarction (MI)
    • Non-fatal stroke
    • Unplanned hospitalization for heart failure (HF)
  • Percentage of Participants With Occurrence of Secondary Renal Composite Endpoint (Core: Active Treatment Phase) [ Time Frame: Time from randomization to the first event (Maximum 50 months) ]
    Occurrence was defined as the first event of the following secondary renal composite endpoint:
    • Onset of end-stage renal disease (ESRD) or death due to renal failure. Onset of ESRD was defined as initiation of dialysis, renal transplantation, or a serum creatinine concentration above 6.0 mg/dL (530 μmol/L), sustained for at least a month.
    • Doubling of baseline serum creatinine concentration, sustained for at least one month. To fulfill the endpoint, the serum creatinine concentration had to be above the upper limit of normal for men and women according to the central laboratory.The upper limit of normal for men is 1.20 mg/dL and for women is 0.91 mg/dL.
  • Percentage of Participants With Occurrence of Secondary Cardiovascular Composite Endpoint (Extension Phase) [ Time Frame: From cut-off date (20Dec2011/End of Treatment (EOT) ) to the first event after cut-off date (9 months in average) ]
    Occurrence was defined as the first event of the following secondary cardiovascular composite endpoint:
    • Cardiovascular (CV) death
    • Resuscitated sudden death
    • Non-fatal myocardial infarction (MI)
    • Non-fatal stroke
    • Unplanned hospitalization for heart failure (HF)
  • Percentage of Participants With Occurrence of Secondary Renal Composite Endpoint (Extension Phase) [ Time Frame: From cut-off date (20Dec2011/End of Treatment (EOT) ) to the first event after cut-off date (9 months in average) ]
    Occurrence was defined as the first event of the following secondary renal composite endpoint:
    • Onset of end-stage renal disease (ESRD) or death due to renal failure. Onset of ESRD was defined as initiation of dialysis, renal transplantation, or a serum creatinine concentration above 6.0 mg/dL (530 μmol/L), sustained for at least a month.
    • Doubling of baseline serum creatinine concentration, sustained for at least one month. To fulfill the endpoint, the serum creatinine concentration had to be above the upper limit of normal for men and women according to the central laboratory. The upper limit of normal for men is 1.20 mg/dL and for women is 0.91 mg/dL.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 25, 2007)
Time from randomization to the first event of the following composite CV endpoint: • Cardiovascular (CV) death • Resuscitated sudden death • Non-fatal myocardial infarction (MI) • Non-fatal stroke • Unplanned hospitalization for heart failu
Current Other Pre-specified Outcome Measures
 (submitted: February 3, 2014)
  • Percentage of Participants With Angioedema/Angioedema-like or Colorectal Events (Core : Active Treatment Phase) [ Time Frame: Time from randomization to the first event (Maximum 50 months) ]
    AEs of special interest were reported according to a post-marketing commitment to Health Authorities and included angioedema/angioedema-like events and colorectal events/ procedures
  • Change From Baseline in Urinary Albumin to Creatinine Ratio (UACR) to Month 6 and to Last Measurement (Core : Active Treatment Phase) [ Time Frame: Baseline, Month 6 , last measurement (maximum at 50 months) ]
    Baseline is the geometric mean of last 3 measurements before visit 3, Post-baseline value is the geometric mean of last 3 measurements during each visit. Change from Baseline = Post - Baseline.
  • Mean Changes in Estimated Glomerular Filtration Rate (eGFR) From Baseline to Month 3 and Month 6 (Core : Active Treatment Phase) [ Time Frame: Baseline to Month 3 and Month 6 ]
    The eGFR calculation was based on the Abbreviated Modification of Diet in Renal Disease (MDRD) Study Equation. Using this method, the applicable MDRD formula to calculate eGFR was as follows: Estimated GFR (mL/min/1.73 m^2) = 175 x (serum creatinine in mg/dL) -1.154 x (Age in years) -0.203 x (0.742 if female) x (1.210 if Black) Mean changes in eGFR from baseline to month 3 and month 6 were included for analysis. The LS Mean and Standard Error were based on an ANCOVA repeated-measure model with treatment, visit, treatment-by-visit and baseline eGFR as effect terms.
  • Percentage of Participants With Angioedema/Angioedema-like Events or Colorectal Events (Extension Phase) [ Time Frame: From cut-off date (20Dec2011/End of Treatment (EOT) ) to the first event after cut-off date (9 months in average) ]
    AEs of special interest were reported according to a post-marketing commitment to Health Authorities and included angioedema/angioedema-like events and colorectal events/ procedures.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints (Core and Extension Phases)
Official Title  ICMJE A Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Determine Whether, in Patients With Type 2 Diabetes at High Risk for Cardiovascular and Renal Events, Aliskiren, on Top of Conventional Treatment, Reduces Cardiovascular and Renal Morbidity and Mortality
Brief Summary

The purpose of this study was to determine whether, in patients with type 2 diabetes and pre-existing disease of the heart and the circulatory system and/or the kidney, aliskiren at a target dose of 300 mg once daily (compared to placebo), on top of conventional treatment, reduces death and disease caused by the heart, the circulatory system and the kidney.

AMENDMENT 4 RATIONALE (MARCH 2012) :

Protocol amendment 4 served to address the data monitoring committee recommendation dated 14 Dec 2011 to discontinue study treatment in all participating patients. It also addressed the subsequent Health Authorities request to implement a 12 month safety follow-up period (actual duration was 9 months in average) post study drug discontinuation.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Type 2 Diabetes Mellitus
  • Cardiovascular Disease
Intervention  ICMJE
  • Drug: Aliskiren
    Aliskiren 150 mg film-coated tablets
  • Drug: Placebo
    Placebo to match aliskiren 150 mg film-coated tablets
Study Arms  ICMJE
  • Experimental: Aliskiren

    In Core (Double Blind) phase, Aliskiren 150 mg once daily (o.d.) for 4 weeks; then patient was uptitrated to 300 mg o.d. at Visit 5/Week 4 (or 150 mg o.d. if patient could not tolerate target dose of study drug). Visits took place at 1, 4 , 5, 8 and 12 weeks after randomization (Visit 3/Week 0). Subsequent visits were planned every three months until end of core phase.

    With the recommendation of Data Monitoring Committee (DMC), after discontinuation of study drug, a follow up was added as Extension Phase (9 months in average) with no active treatment

    Intervention: Drug: Aliskiren
  • Placebo Comparator: Placebo

    In Core (Double Blind) phase, placebo to match aliskiren 150 mg once daily (o.d.) for 4 weeks; from Visit 5/Week 4 placebo to match aliskiren 300 mg o.d. (or placebo to match aliskiren 150 mg if patient could not tolerate target dose of study drug). Visits took place 1, 4 , 5, 8 and 12 weeks after randomization (Visit 3/Week 0). Subsequent visits were planned every three months until end of core phase.

    With the recommendation of Data Monitoring Committee (DMC), after discontinuation of study drug, a follow up was added as Extension Phase (9 months in average) with no active treatment.

    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: February 4, 2013)
8606
Original Estimated Enrollment  ICMJE
 (submitted: October 25, 2007)
8600
Actual Study Completion Date  ICMJE February 2013
Actual Primary Completion Date February 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Type 2 diabetes and at least one of the following:

    • Macroalbuminuria and an eGFR ≥30 mL/min/1.73 m2
    • Microalbuminuria and a reduced kidney function (eGFR eGFR ≥30 and <60 mL/min/1.73 m2)
    • A history of CV disease (previous MI, previous stroke, heart failure, coronary artery disease, history of percutaneous coronary intervention, angiography proven stenosis ≥50% in at least one coronary artery and a reduced kidney function (eGFR ≥30 and <60 mL/min/1.73 m2)
  • Concomitant treatment should follow national guidelines and must include either an Angiotensin-converting-enzyme-inhibitor (ACEi) or an Angiotensin-receptor-blocker (ARB) but not both.

Exclusion Criteria:

  • Type 1 diabetes mellitus
  • Cardiovascular event or procedure ≤ 3 months prior to Visit 1
  • Unstable serum creatinine
  • Hypertension: Mean sitting systolic blood pressure (msSBP) ≥ 135 and < 170 mmHg or Mean sitting diastolic blood pressure (msDBP) ≥ 85 and < 110 mmHg unless treated with at least 3 anti-hypertensive medications
  • Hypertension msSBP ≥ 170 or msDBP ≥ 110 mmHg
  • Baseline Serum Potassium > 5.0 mmol/L
  • Patients who are treated with two renin-angiotensin-aldosterone-system-blockers
  • Patients with NYHA class III or IV heart failure
  • Known renal artery stenosis
  • Previous randomization into the AVOID trial (CSPP100C2201)

EXCLUSION SPECIFIC TO THE SAFETY FOLLOW-UP PERIOD:

- Aliskiren or aliskiren containing fixed combination products must not be used

Other protocol-defined inclusion/exclusion criteria applied

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 35 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Austria,   Belgium,   Brazil,   Canada,   China,   Colombia,   Czech Republic,   Denmark,   Finland,   France,   Germany,   Greece,   Guatemala,   Hungary,   India,   Italy,   Japan,   Korea, Republic of,   Lithuania,   Netherlands,   Norway,   Peru,   Portugal,   Puerto Rico,   Singapore,   Slovakia,   South Africa,   Spain,   Sweden,   Switzerland,   Taiwan,   Thailand,   Turkey,   United Kingdom,   United States,   Venezuela
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00549757
Other Study ID Numbers  ICMJE CSPP100E2337
2007-000860-25 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Study Chair: Novartis Novartis
PRS Account Novartis
Verification Date April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP