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VISTA-16 Trial: Evaluation of Safety and Efficacy of Short-term A-002 Treatment in Subjects With Acute Coronary Syndrome

This study has been terminated.
(Lack of efficacy)
Sponsor:
Information provided by (Responsible Party):
Anthera Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01130246
First received: April 19, 2010
Last updated: October 30, 2012
Last verified: October 2012

April 19, 2010
October 30, 2012
May 2010
March 2012   (final data collection date for primary outcome measure)
Primary Objective of the Study [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
To determine whether 16 weeks of treatment with A-002 plus atorvastatin and standard of care is superior to placebo plus atorvastatin and standard of care for reducing the hazard of the first occurrence of the combined endpoint of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or documented unstable angina with objective evidence of ischemia requiring hospitalization.
The primary objective of the study is to determine whether 16 weeks of treatment with A-002 plus atorvastatin and standard of care is superior to placebo plus atorvastatin and standard of care [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
The primary objective of the study is to determine whether 16 weeks of treatment with A-002 plus atorvastatin and standard of care is superior to placebo plus atorvastatin and standard of care for reducing the hazard of the first occurrence of the combined endpoint of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or documented unstable angina with objective evidence of ischemia requiring hospitalization.
Complete list of historical versions of study NCT01130246 on ClinicalTrials.gov Archive Site
Secondary Objective of the Study [ Time Frame: 2, 4, 8, 16 weeks and 6 months ] [ Designated as safety issue: No ]
To determine whether A-002 plus atorvastatin and standard of care is superior to placebo plus atorvastatin and standard of care for reducing the occurrence of the hazard of the combined endpoint of all-cause mortality, non-fatal myocardial infarction, non-fatal stroke or documented unstable angina with objective evidence of ischemia requiring hospitalization or multiple occurrences of the non-fatal components of the composite primary endpoint.
A secondary objective of the study is to determine whether A-002 plus atorvastatin and standard of care is superior to placebo plus atorvastatin and standard of care [ Time Frame: 2, 4, 8, 16 weeks and 6 months ] [ Designated as safety issue: Yes ]
A secondary objective of the study is to determine whether A-002 plus atorvastatin and standard of care is superior to placebo plus atorvastatin and standard of care for reducing the occurrence of the hazard of the combined endpoint of all-cause mortality, non-fatal myocardial infarction, non-fatal stroke or documented unstable angina with objective evidence of ischemia requiring hospitalization or multiple occurrences of the non-fatal components of the composite primary endpoint.
Not Provided
Not Provided
 
VISTA-16 Trial: Evaluation of Safety and Efficacy of Short-term A-002 Treatment in Subjects With Acute Coronary Syndrome
VISTA-16 Trial: Evaluation of the Safety and Efficacy of Short-Term A-002 Treatment in Subjects With Acute Coronary Syndromes

The objective of this study is to evaluate the safety and efficacy of short-term A-002 treatment on morbidity and mortality when added to atorvastatin and standard of care in subjects with an acute coronary syndrome (ACS).

A double-blind randomized parallel group placebo controlled study in subjects presenting with an ACS. Up to 6500 subjects will be randomized to receive either A-002 500 mg once daily (QD) or placebo tablets in addition to atorvastatin QD and standard of care. Treatment will be 16 weeks in duration. The dose of atorvastatin shall be adjusted after 8 weeks if subject's LDL-C is ≥100 mg/dL, but otherwise must remain stable throughout the16-week duration of study. The survival status for all enrolled subjects will be ascertained 6 months after they complete the study.

Randomization must occur within ≤96 hours of hospitalization for the index ACS event, or if already hospitalized, within ≤96 hours of index event diagnosis. Follow-up visits will occur on Weeks 1, 2, 4, 8, and 16. A 6 month follow-up visit will also occur.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Acute Coronary Syndrome
  • Drug: A-002, varespladib methyl
    A-002 administered once daily in addition to atorvastatin and standard of care
  • Drug: Placebo
    Placebo administered once daily in addition to atorvastatin and standard of care
  • Experimental: A-002 500 mg
    Once daily oral administration
    Intervention: Drug: A-002, varespladib methyl
  • Placebo Comparator: Matched Placebo
    Once daily oral administration
    Intervention: Drug: Placebo
Nicholls SJ, Kastelein JJ, Schwartz GG, Bash D, Rosenson RS, Cavender MA, Brennan DM, Koenig W, Jukema JW, Nambi V, Wright RS, Menon V, Lincoff AM, Nissen SE; VISTA-16 Investigators. Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial. JAMA. 2014 Jan 15;311(3):252-62. doi: 10.1001/jama.2013.282836.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
5189
March 2012
March 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Men and women ≥40 years of age
  2. Written informed consent from the subject
  3. A diagnosis of unstable angina, non-ST-segment elevation myocardial infarction (NSTEMI), or ST-segment elevation myocardial infarction (STEMI)

    Unstable angina is defined as:

    • Chest pain symptomatic of ischemia or angina occurring at rest or on minimal exertion with a pattern of increasing frequency or severity, lasting >10 minutes and consistent with myocardial ischemia within 24 hours prior to hospitalization and
    • New or dynamic ST-segment depression or prominent T-wave inversion changes in at least 2 contiguous leads and
    • In addition subjects meeting the above criteria for unstable angina must also have either troponin I, troponin T or CKMB above the LLD but below the 99th percentile of the upper reference limit (URL) and not due to cardioversion or underlying cardiovascular (CHF, cardiomyopathy) or renal disease

    NSTEMI is defined as:

    • Chest pain symptomatic of ischemia
    • No electrocardiogram (ECG) changes, or ST-depression, or T wave changes(i.e., no new Q waves on serial ECGs)and
    • Increase in cardiac troponin > local limit for the definition of myocardial infarction or increase in CK-MB isoenzyme > URL

    STEMI is defined as:

    • Chest pain symptomatic of ischemia
    • ST segment elevation and associated T wave changes or ST-segment elevation of at least 2 mm in 2 contiguous leads, either of which persisting for longer than 15 minutes and
    • Increase in cardiac troponin > local limit for the definition of myocardial infarction or increase in CK-MB >URL
  4. All subjects must have the presence of at least one of the following risk factors:

    • Diabetes Mellitus or
    • Presence of any 3 of the following characteristics of metabolic syndrome

      • Waist circumference >102 cm in males, >88 cm in females
      • Serum triglycerides ≥150 mg/dL (≥1.7 mmol/L)
      • HDL-C <40 mg/dL (<1 mmol/L) in males, <50 mg/dL (<1.3 mmol/L) in females
      • Blood pressure ≥130/85 mmHg
      • Plasma glucose ≥110 mg/dL (≥6.1 mmol/L) or
    • history of cerebrovascular disease (stroke or TIA) or
    • history of peripheral vascular disease or
    • previous CABG or
    • previous documented myocardial infarction or
    • previous coronary revascularization
  5. Subjects must be randomized within ≤96 hours of hospital admission for the index event, or if already hospitalized, within ≤96 hours of index event diagnosis
  6. Revascularization, if required or planned, must occur prior to randomization

Exclusion Criteria:

  1. Subjects enrolled in another experimental (interventional)protocol within the past 30 days prior to Screening.
  2. Subjects treated for cancer within the previous 5 years except for skin basal cell carcinoma or carcinoma in situ of the cervix, with measures other than a minor, complete surgical excision or radiation therapy (e.g. chemotherapy)
  3. The presence of any severe liver disease with cirrhosis, active hepatitis, active chronic hepatitis, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 x ULN, biliary obstruction with hyperbilirubinemia (total bilirubin >2 x ULN)
  4. Active cholecystitis, gall bladder symptoms, or any hepatobiliary abnormalities
  5. The presence of severe renal impairment (creatinine clearance [CrCl] <30 mL/min or creatinine >3 x ULN),nephrotic syndrome, or subjects undergoing dialysis
  6. Uncontrolled diabetes mellitus (known hemoglobin A1c [HbA1c] >11% within the last 1 month prior to Screening)
  7. Females who are nursing, pregnant, or intend to become pregnant during the time of the study, or females of childbearing potential who have a positive pregnancy test during screening evaluation. Women of child-bearing potential must also use a reliable method of birth control during the study and for 1 month following completion of therapy. A reliable method for this study is defined as one of the following: oral or injectable contraceptives, intrauterine device (IUD), contraceptive implants, tubal ligation, hysterectomy, a double barrier method (diaphragm with spermicidal foam or jelly, or a condom).
  8. Subjects who have a history of alcohol or drug abuse within 1 year of study entry
  9. Subjects living too far from participating center or unable to return for follow-up visits
  10. Subjects who in the opinion of the Investigator are a poor medical or psychiatric risk for therapy with an investigational drug, are unreliable, or have an incomplete understanding of the study which may affect their ability to take drugs as prescribed or comply with instructions
  11. Known human immunodeficiency virus (HIV), Hepatitis B virus (HBV), Hepatitis C virus (HCV), or tuberculosis infection
  12. Acute bacterial, fungal or viral infection
  13. Subjects currently taking drugs that are potent inhibitors of cytochrome P450 unless they can be withdrawn
  14. Subjects with New York Heart Association (NYHA) Class III or IV heart failure, or if known, left ventricular ejection fraction (LVEF) <30
  15. Subjects with moderate or severe aortic stenosis, aortic regurgitation, mitral stenosis or mitral regurgitation
  16. Ventricular arrhythmias requiring chronic drug treatment or implantable cardioverter-defibrillator (ICD)
  17. Subjects with no stenosis or stenosis <50% on angiography, if known
  18. Subjects with a pacemaker or persistent left bundle branch block (LBBB)
  19. Fasting triglyceride levels of ≥400 mg/dL (4.5 mmol/L)
  20. Subjects who have a history of statin intolerance or a significant myopathy or rhabdomyolysis with any lipid altering drugs
  21. Subjects currently treated with the maximum labeled dose of a statin and not at LDL-C target for their level of risk as defined by NCEP ATP III
Both
40 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Canada,   Czech Republic,   Georgia,   Germany,   Hungary,   India,   Italy,   Korea, Republic of,   Lebanon,   Netherlands,   New Zealand,   Poland,   Russian Federation,   Spain,   Ukraine
 
NCT01130246
AN-CVD2233
Yes
Anthera Pharmaceuticals
Anthera Pharmaceuticals
Not Provided
Not Provided
Anthera Pharmaceuticals
October 2012

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