Primary Prevention of Major Adverse Cardiac Events (MACE) With Standard and Intensive Statin Treatment in Patients With Diabetes: Survival and Cardiovascular Event Assessments (POSITIVE)

This study has been terminated.
(With recommendation from IDMC, Steering Committee terminated this trial due to ethical concerns raised by J-ART study.)
Sponsor:
Information provided by:
Positive Trial Group
ClinicalTrials.gov Identifier:
NCT01173939
First received: July 27, 2010
Last updated: May 30, 2011
Last verified: November 2010
  Purpose

The study is being conducted to compare the effect of standard treatment (target LDL-C level: <120 mg/dL (JASGL 2007 target level)) and intensive treatment (target LDL-C level: <70 mg/dL) in the prevention of major adverse cardiac events (MACE) in hypercholesterolemia patients with concomitant type 2 diabetes and hypertension.


Condition Intervention
Hypercholesterolemia
Type 2 Diabetes
Hypertension
Drug: Pravastatin
Drug: Rosuvastatin

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Primary Prevention of MACE With Standard and Intensive Statin Treatment in Hypercholesterolemia Patients With Concomitant Diabetes and Hypertension

Resource links provided by NLM:


Further study details as provided by Positive Trial Group:

Primary Outcome Measures:
  • MACE (time to event): MACE (time to event): myocardial infarction, unstable angina, cardiovascular death, revascularization, fatal/nonfatal cerebrovascular accident, peripheral arteriopathy, aortic event [ Time Frame: At baseline ] [ Designated as safety issue: No ]
  • MACE (time to event): MACE (time to event): myocardial infarction, unstable angina, cardiovascular death, revascularization, fatal/nonfatal cerebrovascular accident, peripheral arteriopathy, aortic event [ Time Frame: 1 month after treatment initiation ] [ Designated as safety issue: No ]
  • MACE (time to event): MACE (time to event): myocardial infarction, unstable angina, cardiovascular death, revascularization, fatal/nonfatal cerebrovascular accident, peripheral arteriopathy, aortic event [ Time Frame: 3 month after treatment initiation ] [ Designated as safety issue: No ]
  • MACE (time to event): MACE (time to event): myocardial infarction, unstable angina, cardiovascular death, revascularization, fatal/nonfatal cerebrovascular accident, peripheral arteriopathy, aortic event [ Time Frame: 6 month after treatment initiation ] [ Designated as safety issue: No ]
  • MACE (time to event): MACE (time to event): myocardial infarction, unstable angina, cardiovascular death, revascularization, fatal/nonfatal cerebrovascular accident, peripheral arteriopathy, aortic event [ Time Frame: 12 month after treatment initiation ] [ Designated as safety issue: No ]
  • MACE (time to event): MACE (time to event): myocardial infarction, unstable angina, cardiovascular death, revascularization, fatal/nonfatal cerebrovascular accident, peripheral arteriopathy, aortic event [ Time Frame: 36 month after treatment initiation ] [ Designated as safety issue: No ]
  • MACE (time to event): MACE (time to event): myocardial infarction, unstable angina, cardiovascular death, revascularization, fatal/nonfatal cerebrovascular accident, peripheral arteriopathy, aortic event [ Time Frame: At the end of the study or discontinuation up to 4 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Prevention of individual MACE [ Time Frame: At baseline ] [ Designated as safety issue: Yes ]
  • Prevention of MACE(combination of each category) [ Time Frame: At baseline ] [ Designated as safety issue: Yes ]
  • Prevention, frequency and distribution of type of the following non-MACE cardiac and cerebrovascular events during the study period: heart failure requiring hospitalization, transient ischemic attack (TIA), abnormal ankle-brachial index (abnormal ABI) [ Time Frame: At baseline ] [ Designated as safety issue: Yes ]
  • Frequency and distribution of type of MACE during the study period Including correlation with LDL-C, HDL-C and LDL-C/HDL-C ratio (hereafter referred to as "L/H ratio") [ Time Frame: At baseline ] [ Designated as safety issue: Yes ]
  • Frequency and distribution of type of deaths during the study period [ Time Frame: At baseline ] [ Designated as safety issue: Yes ]
  • Frequency and distribution of type of hospitalizations during the study period [ Time Frame: At baseline ] [ Designated as safety issue: Yes ]
  • Frequency of other events (malignancy, dementia, need of nursing care) [ Time Frame: At baseline ] [ Designated as safety issue: Yes ]
  • Frequency and type of adverse events [ Time Frame: At baseline ] [ Designated as safety issue: Yes ]
  • Prevention of individual MACE [ Time Frame: 1 month after treatment initiation ] [ Designated as safety issue: Yes ]
  • Prevention of individual MACE [ Time Frame: 3 month after treatment initiation ] [ Designated as safety issue: Yes ]
  • Prevention of individual MACE [ Time Frame: 6 month after treatment initiation ] [ Designated as safety issue: Yes ]
  • Prevention of individual MACE [ Time Frame: 12 month after treatment initiation ] [ Designated as safety issue: Yes ]
  • Prevention of individual MACE [ Time Frame: 36 month after treatment initiation ] [ Designated as safety issue: Yes ]
  • Prevention of individual MACE [ Time Frame: At the end of the study (or discontinuation) ] [ Designated as safety issue: Yes ]
  • Prevention of MACE(combination of each category) [ Time Frame: 1 month after treatment initiation ] [ Designated as safety issue: Yes ]
  • Prevention of MACE(combination of each category) [ Time Frame: 3 month after treatment initiation ] [ Designated as safety issue: Yes ]
  • Prevention of MACE(combination of each category) [ Time Frame: 6 month after treatment initiation ] [ Designated as safety issue: Yes ]
  • Prevention of MACE(combination of each category) [ Time Frame: 12 month after treatment initiation ] [ Designated as safety issue: Yes ]
  • Prevention of MACE(combination of each category) [ Time Frame: 36 month after treatment initiation ] [ Designated as safety issue: Yes ]
  • Prevention of MACE(combination of each category) [ Time Frame: At the end of the study (or discontinuation) ] [ Designated as safety issue: Yes ]
  • Prevention, frequency and distribution of type of the following non-MACE cardiac and cerebrovascular events during the study period: heart failure requiring hospitalization, transient ischemic attack (TIA), abnormal ankle-brachial index (abnormal ABI) [ Time Frame: 1 month after treatment initiation ] [ Designated as safety issue: Yes ]
  • Prevention, frequency and distribution of type of the following non-MACE cardiac and cerebrovascular events during the study period: heart failure requiring hospitalization, transient ischemic attack (TIA), abnormal ankle-brachial index (abnormal ABI) [ Time Frame: 3 month after treatment initiation ] [ Designated as safety issue: Yes ]
  • Prevention, frequency and distribution of type of the following non-MACE cardiac and cerebrovascular events during the study period: heart failure requiring hospitalization, transient ischemic attack (TIA), abnormal ankle-brachial index (abnormal ABI) [ Time Frame: 6 month after treatment initiation ] [ Designated as safety issue: Yes ]
  • Prevention, frequency and distribution of type of the following non-MACE cardiac and cerebrovascular events during the study period: heart failure requiring hospitalization, transient ischemic attack (TIA), abnormal ankle-brachial index (abnormal ABI) [ Time Frame: 12 month after treatment initiation ] [ Designated as safety issue: Yes ]
  • Prevention, frequency and distribution of type of the following non-MACE cardiac and cerebrovascular events during the study period: heart failure requiring hospitalization, transient ischemic attack (TIA), abnormal ankle-brachial index (abnormal ABI) [ Time Frame: 36 month after treatment initiation ] [ Designated as safety issue: Yes ]
  • Prevention, frequency and distribution of type of the following non-MACE cardiac and cerebrovascular events during the study period: heart failure requiring hospitalization, transient ischemic attack (TIA), abnormal ankle-brachial index (abnormal ABI) [ Time Frame: At study completion up to 4 years ] [ Designated as safety issue: Yes ]
  • Frequency and distribution of type of MACE during the study period Including correlation with LDL-C, HDL-C and LDL-C/HDL-C ratio (hereafter referred to as "L/H ratio") [ Time Frame: 1 month after treatment initiation ] [ Designated as safety issue: Yes ]
  • Frequency and distribution of type of MACE during the study period Including correlation with LDL-C, HDL-C and LDL-C/HDL-C ratio (hereafter referred to as "L/H ratio") [ Time Frame: 3 month after treatment initiation ] [ Designated as safety issue: Yes ]
  • Frequency and distribution of type of MACE during the study period Including correlation with LDL-C, HDL-C and LDL-C/HDL-C ratio (hereafter referred to as "L/H ratio") [ Time Frame: 6 month after treatment initiation ] [ Designated as safety issue: Yes ]
  • Frequency and distribution of type of MACE during the study period Including correlation with LDL-C, HDL-C and LDL-C/HDL-C ratio (hereafter referred to as "L/H ratio") [ Time Frame: 12 month after treatment initiation ] [ Designated as safety issue: Yes ]
  • Frequency and distribution of type of MACE during the study period Including correlation with LDL-C, HDL-C and LDL-C/HDL-C ratio (hereafter referred to as "L/H ratio") [ Time Frame: 36 month after treatment initiation ] [ Designated as safety issue: Yes ]
  • Frequency and distribution of type of MACE during the study period Including correlation with LDL-C, HDL-C and LDL-C/HDL-C ratio (hereafter referred to as "L/H ratio") [ Time Frame: At the end of the study or discontinuation up to 4 years ] [ Designated as safety issue: Yes ]
  • Frequency and distribution of type of deaths during the study period [ Time Frame: 1 month after treatment initiation ] [ Designated as safety issue: Yes ]
  • Frequency and distribution of type of deaths during the study period [ Time Frame: 3 month after treatment initiation ] [ Designated as safety issue: Yes ]
  • Frequency and distribution of type of deaths during the study period [ Time Frame: 6 month after treatment initiation ] [ Designated as safety issue: Yes ]
  • Frequency and distribution of type of deaths during the study period [ Time Frame: 12 month after treatment initiation ] [ Designated as safety issue: Yes ]
  • Frequency and distribution of type of deaths during the study period [ Time Frame: 36 month after treatment initiation ] [ Designated as safety issue: Yes ]
  • Frequency and distribution of type of deaths during the study period [ Time Frame: At the end of the study or discontinuation up to 4 years ] [ Designated as safety issue: Yes ]
  • Frequency and distribution of type of hospitalizations during the study period [ Time Frame: 1 month after treatment initiation ] [ Designated as safety issue: Yes ]
  • Frequency and distribution of type of hospitalizations during the study period [ Time Frame: 3 month after treatment initiation ] [ Designated as safety issue: Yes ]
  • Frequency and distribution of type of hospitalizations during the study period [ Time Frame: 6 month after treatment initiation ] [ Designated as safety issue: Yes ]
  • Frequency and distribution of type of hospitalizations during the study period [ Time Frame: 12 month after treatment initiation ] [ Designated as safety issue: Yes ]
  • Frequency and distribution of type of hospitalizations during the study period [ Time Frame: 36 month after treatment initiation ] [ Designated as safety issue: Yes ]
  • Frequency and distribution of type of hospitalizations during the study period [ Time Frame: At the end of the study or discontinuation up to 4 years ] [ Designated as safety issue: Yes ]
  • Frequency of other events (malignancy, dementia, need of nursing care) [ Time Frame: 1 month after treatment initiation ] [ Designated as safety issue: Yes ]
  • Frequency of other events (malignancy, dementia, need of nursing care) [ Time Frame: 3 month after treatment initiation ] [ Designated as safety issue: Yes ]
  • Frequency of other events (malignancy, dementia, need of nursing care) [ Time Frame: 6 month after treatment initiation ] [ Designated as safety issue: Yes ]
  • Frequency of other events (malignancy, dementia, need of nursing care) [ Time Frame: 12 month after treatment initiation ] [ Designated as safety issue: Yes ]
  • Frequency of other events (malignancy, dementia, need of nursing care) [ Time Frame: 36 month after treatment initiation ] [ Designated as safety issue: Yes ]
  • Frequency of other events (malignancy, dementia, need of nursing care) [ Time Frame: At the end of the study or discontinuation up to 4 years ] [ Designated as safety issue: Yes ]
  • Frequency and type of adverse events [ Time Frame: 1 month after treatment initiation ] [ Designated as safety issue: Yes ]
  • Frequency and type of adverse events [ Time Frame: 3 month after treatment initiation ] [ Designated as safety issue: No ]
  • Frequency and type of adverse events [ Time Frame: 6 month after treatment initiation ] [ Designated as safety issue: Yes ]
  • Frequency and type of adverse events [ Time Frame: 12 month after treatment initiation ] [ Designated as safety issue: Yes ]
  • Frequency and type of adverse events [ Time Frame: 36 month after treatment initiation ] [ Designated as safety issue: Yes ]
  • Frequency and type of adverse events [ Time Frame: At the end of the study or discontinuation up to 4 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 10000
Study Start Date: July 2010
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Active comparator: Standard Pravastatin Group Drug: Pravastatin
5 mg/day or 10 mg/day of pravastatin will be administered orally for 36 months, with a follow-up period of one month. If the target LDL-C level is not attained after one month of treatment, the steps will be taken to reduce the LDL-C to the target level of <120 mg/dL (JASGL 2007 target level) as quickly as possible. (Maximum dose increase of pravastatin: 20 mg/day)
Active Comparator: Intensive Rosuvastatin Group Drug: Rosuvastatin
5 mg/day or 10 mg/day of rosuvastatin will be administered orally for 36 months based on the LDL-C level of the subject, with a follow-up period of one month. If the target LDL-C level is not attained after one month of treatment, the steps will be taken to reduce the LDL-C to the target level of <70 mg/dL as quickly as possible. (Maximum dose increase to rosuvastatin: 20 mg/day)

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients meeting the following inclusion criteria will be included in the study:

  1. Patients giving voluntary written consent to participate in the study
  2. Male or female patients 50 years of age or older (at informed consent)
  3. Hypercholesterolemia patients (Untreated patients: LDL-C level ≥140 mg/dL; treated patients: LDL-C level ≥120 mg/dL)
  4. Type 2 diabetes patients (HbA1c level ≥6.1% (JDS criteria), with or without history of drug therapy)
  5. Hypertension patients (SBP ≥130 mmHg or DBP ≥80 mmHg, with or without history of drug therapy)
  6. Patients with two or more of the following risk factors

    • Male
    • 65 years of age or older
    • Smoker
    • L/H ratio: ≥3.0 •HbA1c level: ≥8.0%
    • Left ventricular hypertrophy
    • First- or second-degree family history of MACE
    • Microalbuminuria (quantitative testing: ≥30 mg/dL), proteinuria (qualitative testing: + or higher) or eGFR (<60 mL/min/1.73 m2)

Exclusion Criteria:

Patients meeting the following criteria will be excluded from the study:

  1. Patients receiving rosuvastatin, pitavastatin, or atorvastatin therapy within one month prior to informed consent
  2. Patients judged to have familial hypercholesterolemia
  3. Patients with a serum triglyceride level of ≥400 mg/dL
  4. Patients with a history of myocardial infarction
  5. Patients with a history of coronary revascularization (PCI or CABG)
  6. Patients with a history of treatment of unstable angina
  7. Patients with a history of cerebrovascular accident (excluding asymptomatic lacunar infarction)
  8. Heart failure patients
  9. Patients with a history of hypersensitivity to statins
  10. Patients with a history of drug-induced myopathy
  11. Patients with poorly controlled arrhythmia
  12. Patients with severe liver or kidney disease
  13. Patients with serious concurrent disease, such as malignancy, or patients with severely limited lifespan
  14. Patients who are or may be pregnant
  15. Patients judged by the investigators to be ineligible for participation in the study for any other reason
  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: NCT01173939

  Show 317 Study Locations
Sponsors and Collaborators
Positive Trial Group
  More Information

No publications provided

Responsible Party: Hisao Ogawa, Department of Cardiovascular Medicine, Faculty of Graduate School of Medical Sciences, Kumamoto University
ClinicalTrials.gov Identifier: NCT01173939     History of Changes
Other Study ID Numbers: 0035
Study First Received: July 27, 2010
Last Updated: May 30, 2011
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Positive Trial Group:
Hypercholesterolemia with concomitant type 2 diabetes and hypertension

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Hypercholesterolemia
Hypertension
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Vascular Diseases
Cardiovascular Diseases
Pravastatin
Rosuvastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014