Clinical trial NCT01356992: Patients With High-risk Acute Coronary Syndrome Without ST-segment Elevation
Official title: A Multicenter, Randomized, Open-label, Non-inferiority Phase III Study, Between Low-Molecular Weight Heparins, Versa® (Enoxaparin - Eurofarma) and Clexane® (Enoxaparin - Sanofi-Aventis), in Patients With High-risk Acute Coronary Syndrome Without ST-segment Elevation.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Non ST Segment Elevation Myocardial Infarction
Unstable Angina
Keywords: non-inferiority phase III study
Low-Molecular Weight Heparin
Versa® (enoxaparin - Eurofarma)
Clexane® (enoxaparin - Sanofi-Aventis)
Acute coronary syndrome without ST-segment elevation
Lead sponsor: Eurofarma Laboratorios S.A.
Sponsor class: INDUSTRY
First posted: 2011-05-20
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This non-inferiority study aims at comparing Versa® to the reference enoxaparin (Clexane®, Sanofi-Aventis) in patients with high-risk unstable angina and NSTEMI. The main justification is the search for scientific evidence to prove the Versa® effectiveness for this new therapeutic indication, since it is a product with potential for reducing costs, with effectiveness and safety comparable to the reference drug.

Detailed description: To be included in this study, the eligible patients must meet all criteria below:

IC signature; The research subject must agree about following all instructions and perform the procedures and study visits; Men and women over the age of 18 and below the age of 75; History of angina of rest with a minimum duration of 20 minutes in the last 24 hours at the beginning and at least for 10 days.

Patient Randomization up to 6 hours after the arrival at the emergency sector.

Evidence of NSTEMI or unstable angina due to one or more of the following criteria:

1. Dynamic alterations on the T-wave (ST-segment depression or elevation \> 1 mm, and/or T-wave inversions which are solved at least partially when the symptoms are relieved) or 2. Unevenly ST-segment (depression or elevation) in a transitional way under continuous derivations (V1+V2 or V3+V4 or V5+V6 or D1+AVL or D2+D3+AVF) or 3. Biochemical alteration on the myocardial necrosis markers (CKMB mass, troponin T or I and CPK), with the appearance of enzymatic curve, characterizing myocardial injury or 5. Pulmonary Edema; or 6. Angina associated to murmur of mitral regurgitation; or 7. Angina with heart sound to cardiac auscultation or throes; or 8. Angina with hypotension;

The patients who meet anyone of the criteria below will not be eligible for the study:

12-derivation-ECG with persistent ST-segment elevation; Diagnosis of angina by secondary cause (e.g., anemia, fever, hypovolemia, dehydration, use of cocaine); Use of non-fractionated heparin or low-molecular weight heparin in the prior 48 to the randomization; Concomitant diseases, such as severe renal failure (creatinine clearance lower than 30ml/min.) and hepatic, or other significant comorbidities under investigator judgment; Recent hemorrhagic cerebrovascular accident (last 12 months); Patient scheduled for cardiac surgery of myocardial revascularization; Use of drugs, alcohol abuse; Pregnancy or lactation; Recent neurosurgery or ophthalmic surgery (last 3 months); History or diagnosis of coagulopathy; Medical record containing allergy, hypersensibility or intolerance to any of the drug components to be used on this study, which is judged as clinically significant in the main investigator's opinion; Recent participation (last 12 months) in a clinical study.

Eligibility criteria: Inclusion Criteria:

* ICF signature;
* The research subject must agree about following all instructions and perform the procedures and study visits;
* Men and women over the age of 18 and below the age of 75;
* History of angina of rest with a minimum duration of 20 minutes in the last 24 hours at the beginning and at least for 10 days.
* Patient Randomization up to 6 hours after the arrival at the emergency sector.
* Evidence of NSTEMI or unstable angina due to one or more of the following criteria:

  1. Dynamic alterations on the T-wave (ST-segment depression or elevation \> 1 mm, and/or T-wave inversions which are solved at least partially when the symptoms are relieved) or 2. Unevenly ST-segment (depression or elevation) in a transitional way under continuous derivations (V1+V2 or V3+V4 or V5+V6 or D1+AVL or D2+D3+AVF) or 3. Biochemical alteration on the myocardial necrosis markers (CKMB mass, troponin T or I and CPK), with the appearance of enzymatic curve, characterizing myocardial injury or 5. Pulmonary Edema; or 6. Angina associated to murmur of mitral regurgitation; or 7. Angina with heart sound to cardiac auscultation or throes; or 8. Angina with hypotension;

Exclusion Criteria:

* 12-derivation-ECG with persistent ST-segment elevation;
* Diagnosis of angina by secondary cause (e.g., anemia, fever, hypovolemia, dehydration, use of cocaine);
* Use of non-fractionated heparin or low-molecular weight heparin in the prior 48 to the randomization;
* Concomitant diseases, such as severe renal failure (creatinine clearance lower than 30ml/min.) and hepatic, or other significant comorbidities under investigator judgment;
* Recent hemorrhagic cerebrovascular accident (last 12 months);
* Patient scheduled for cardiac surgery of myocardial revascularization;
* Use of drugs, alcohol abuse;
* Pregnancy or lactation;
* Recent neurosurgery or ophthalmic surgery (last 3 months);
* History or diagnosis of coagulopathy;
* Medical record containing allergy, hypersensibility or intolerance to any of the drug components to be used on this study, which is judged as clinically significant in the main investigator's opinion;
* Recent participation (last 12 months) in a clinical study.

Primary outcomes:
measure: Frequency of death and infarction within 30 days after the admission in emergency
timeFrame: 30 days after the admission in emergency
Secondary outcomes:
measure: Comparing the effectiveness and safety of the two formulations in patients with NSTE-ACS and high-risk ones
timeFrame: 30 days after the admission in emergency
Other outcomes:
Locations:
city: Salvador
country: Brazil
state: Bahia
city: Belo Horizonte
country: Brazil
state: Minas Gerais
city: Porto Alegre
country: Brazil
state: Rio Grande do Sul
city: São Jose do Rio Preto
country: Brazil
state: São Paulo
city: São Paulo
country: Brazil
Study officials:
References: