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Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints (Core and Extension Phases) (ALTITUDE)

This study has been terminated.
(Lack of benefit and safety concern)
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00549757
First received: October 24, 2007
Last updated: April 1, 2014
Last verified: April 2014
Results First Received: February 3, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Conditions: Type 2 Diabetes Mellitus
Cardiovascular Disease
Interventions: Drug: Aliskiren
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Per data monitoring committee (DMC) recommendation all patients were required to permanently stop study medication by 06Jan2012. A follow-up period (actual duration, 9 months in average) post study drug discontinuation on 7590 patients was implemented upon request of Health Authority following the recommendation of DMC to cease study treatment.

Reporting Groups
  Description
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.

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.


Participant Flow for 2 periods

Period 1:   Active Treatment Phase: Max. 50 Months
    Aliskiren     Placebo  
STARTED     4296 [1]   4310  
Full Analysis Set     4274     4287  
Safety Set     4272     4285  
COMPLETED     0     0  
NOT COMPLETED     4296     4310  
Adverse Event                 590                 462  
Abnormal laboratory value(s)                 98                 58  
Abnormal test procedure result(s)                 7                 7  
Unsatisfactory therapeutic effect                 47                 53  
Subject withdrew consent                 38                 38  
Lost to Follow-up                 41                 29  
Administrative problems                 2857                 3019  
Death                 188                 200  
Patient's request                 353                 380  
Incorrect Entry                 69                 55  
Missing data                 8                 9  
[1] "Started" indicates randomized patients.

Period 2:   Extension Period (in Average 9 Months)
    Aliskiren     Placebo  
STARTED     3773 [1]   3817 [1]
COMPLETED     3148     3182  
NOT COMPLETED     625     635  
Death                 143                 136  
Lost to Follow-up                 52                 47  
Withdrawal by Subject                 9                 16  
Patient's request                 421                 436  
[1] As explained in "pre-assignment detail", follow up was made after drug discontinuation



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set (FAS) : All patients randomized except mis-randomized patients who did not receive study drug.

Reporting Groups
  Description
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.

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.

Total Total of all reporting groups

Baseline Measures
    Aliskiren     Placebo     Total  
Number of Participants  
[units: participants]
  4274     4287     8561  
Age  
[units: Years]
Mean ± Standard Deviation
  64.6  ± 9.62     64.4  ± 9.87     64.5  ± 9.75  
Gender  
[units: participants]
     
Female     1393     1342     2735  
Male     2881     2945     5826  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   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) ]

2.  Primary:   Percentage of Participants With Cardiovascular (CV) Death (Core: Active Treatment Phase)   [ Time Frame: Time from randomization to the first event (Maximum 50 months) ]

3.  Primary:   Percentage of Participants With Resuscitated Sudden Death (Core: Active Treatment Phase)   [ Time Frame: Time from randomization to the first event (Maximum 50 Months) ]

4.  Primary:   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) ]

5.  Primary:   Percentage of Participants With Fatal/Non-fatal Stroke (Core: Active Treatment Phase)   [ Time Frame: Time from randomization to the first event (Maximum 50 Months) ]

6.  Primary:   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) ]

7.  Primary:   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) ]

8.  Primary:   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) ]

9.  Primary:   Percentage of Participants With All Cause Mortality (Core: Active Treatment Phase)   [ Time Frame: Time from randomization to the first event (Maximum 50 months) ]

10.  Primary:   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) ]

11.  Primary:   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) ]

12.  Primary:   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) ]

13.  Primary:   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) ]

14.  Primary:   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) ]

15.  Primary:   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) ]

16.  Primary:   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) ]

17.  Primary:   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) ]

18.  Primary:   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) ]

19.  Secondary:   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) ]

20.  Secondary:   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) ]

21.  Secondary:   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) ]

22.  Secondary:   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) ]

23.  Other Pre-specified:   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) ]

24.  Other Pre-specified:   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) ]

25.  Other Pre-specified:   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 ]

26.  Other Pre-specified:   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) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
phone: 862-778-8300
e-mail: trialandresults.registries@novartis.com


No publications provided by Novartis

Publications automatically indexed to this study:

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00549757     History of Changes
Other Study ID Numbers: CSPP100E2337, 2007-000860-25
Study First Received: October 24, 2007
Results First Received: February 3, 2014
Last Updated: April 1, 2014
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Austria: Federal Office for Safety in Health Care
Belgium: Federal Agency for Medicinal Products and Health Products
Brazil: Ministry of Health
Canada: Health Canada
China: Food and Drug Administration
Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Czech Republic: State Institute for Drug Control
Denmark: Danish Medicines Agency
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Greece: National Organization of Medicines
Guatemala: Ministry of Public Health and Social Assistance
Hungary: National Institute of Pharmacy
India: Central Drugs Standard Control Organization
Italy: National Institute of Health
Japan: Pharmaceuticals and Medical Devices Agency
Korea: Food and Drug Administration
Lithuania: State Medicine Control Agency - Ministry of Health
Netherlands: Medicines Evaluation Board (MEB)
Norway: Norwegian Medicines Agency
Peru: General Directorate of Pharmaceuticals, Devices, and Drugs
Portugal: National Pharmacy and Medicines Institute
Singapore: Center for Drug Administration
Slovakia: State Institute for Drug Control
South Africa: Medicines Control Council
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Switzerland: Swissmedic
Taiwan: Department of Health
Thailand: Ministry of Public Health
Turkey: General Directorate of Pharmaceuticals and Pharmacy
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Venezuela: Ministry of Health and Social Development