Clinical trial NCT00743925: FRANCIS-ACS Trial: A Study of the Safety and Efficacy of A 002 in Subjects With Acute Coronary Syndromes
Official title: FRANCIS-ACS Trial: A Study of the Safety and Efficacy of A 002 in Subjects With Acute Coronary Syndromes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Coronary Syndrome
Keywords: Unstable Angina
STEMI
NSTEMI
ACS
Acute Coronary Syndrome
C14.280.647.124
C14.280.647.500
Lead sponsor: Anthera Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2008-08-29
Enrollment: 625
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this study is to evaluate the safety and efficacy of A 002 when added to high dose atorvastatin in subjects with an acute coronary syndrome (ACS)

Detailed description: This is a double-blind randomized parallel group placebo controlled study in subjects presenting with an ACS. Subjects will be randomized to receive either A 002 500 mg once daily (QD) or placebo tablets in addition to 80 mg atorvastatin QD.

Randomization must occur within ≤96 hours of hospital admission for the index ACS event, or, if already hospitalized, within ≤96 hours of index event diagnosis. Follow-up visits will occur at Weeks 2, 4, 8, 12, 16, 20, and 24 post-randomization; and monthly thereafter until study completion.

All enrolled subjects will remain on treatment until all subjects have been treated for a minimum of 24 weeks or until the occurrence of a Major Adverse Cardiac Event (MACE). At that point, all active subjects (those who have not early withdrawn or those that have not already had a MACE) will be brought in for a Final Study Visit. Subjects who complete the Final Study Visit may be eligible to enroll in an open-label extension study for up to 2 years total study drug exposure.

Eligibility criteria: Inclusion Criteria:

* Men and women ≥18 years of age
* A diagnosis of unstable angina, NSTEMI, or STEMI
* Any one of the following criteria: Diabetes, CRP ≥2 mg/L, or metabolic syndrome
* Subjects must be randomized within 96 hours of the index event
* Percutaneous revascularization, if required or planned, must occur prior to randomization

Exclusion Criteria:

- Subjects must NOT meet any of the following exclusion criteria:

* Subjects enrolled in another experimental (interventional) protocol within the past 30 days prior to Screening.
* 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 (e.g., chemotherapy), or radiation therapy.
* The presence of severe liver disease with cirrhosis, recent active hepatitis, active chronic hepatitis, ALT or AST \>3 x ULN, biliary obstruction with hyperbilirubinemia (total bilirubin \>2 x ULN)
* Active cholecystitis, gall bladder symptoms, or potential hepato-biliary abnormalities
* The presence of severe renal impairment (CrCl \<30 mL/min or creatinine \>3 x ULN), nephrotic syndrome, or patients undergoing dialysis
* Uncontrolled diabetes mellitus (HbA1c \>11% within the last 1 month prior to Screening)
* Females who are nursing, pregnant, or intend to become pregnant during the time of the study, or females of child-bearing 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, IUD, contraceptive implants, tubal ligation, hysterectomy, a barrier method (diaphragm with spermicidal foam or jelly, or a condom).
* Subjects who have a history of alcohol or drug abuse within 1 year of study entry
* Subjects living too far from participating center or unable to return for follow-up visits
* 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
* Known HIV, Hepatitis B or C virus, or tuberculosis infection
* Acute bacterial, fungal or viral infection
* Any current statin therapy at maximum recommended dosage. For atorvastatin, fluvastatin, lovastatin, pravastatin and simvastatin 80 mg QD at the time of the index event and for rosuvastatin 20 mg QD to 40 mg QD
* Drugs that are potent inhibitors of cytochrome P450 unless they can be withdrawn
* Subjects with NYHA Class III or IV heart failure, or LVEF \<30
* Subjects with moderate or severe aortic stenosis, aortic regurgitation, mitral stenosis or mitral regurgitation
* Ventricular arrhythmias requiring chronic drug treatment or ICD
* Subjects with no stenosis or stenosis \<50% on angiography
* Subjects with a pacemaker or persistent LBBB
* LDL-C \>200 mg/dL (5.2 mmol/L)
* Fasting triglyceride levels of ≥400 mg/dL (4.5 mmol/L)

Primary outcomes:
measure: Mean percent changes in LDL hs-CRP, sPLA2 and other biomarkers will be compared between the 2 treatment groups.
timeFrame: 8 Weeks
Secondary outcomes:
measure: The occurrence of MACEs will be examined for any treatment-related trends at study completion.
timeFrame: End of Study
Other outcomes:
Locations:
city: Tbilisi
country: Georgia
facility: Cardiological hospital of The Patriarchate of all Georgia
city: Tbilisi
country: Georgia
facility: Tbilisi State Medical University, Al. Aladashvili University Clinic
city: Tbilisi
country: Georgia
facility: Cardio Reanimation Centre
city: Tbilisi
country: Georgia
facility: Cardiological Clinic "Guli"
city: Tbilisi
country: Georgia
facility: Tbilisi LTD Cardiology Clinic
city: Tbilisi
country: Georgia
facility: Emergency Cardiology Center by acad. G. Chapidze
city: Tbilisi
country: Georgia
facility: National Center of Therapy
city: Tbilisi
country: Georgia
facility: Multiprofile Clinical Hospital of Tbilisi #2
city: Tbilisi
country: Georgia
facility: Diagnostic Services Clinic
city: Tbilisi
country: Georgia
facility: Limited Company "ADAPTI" The Clinic of Angiocardiology "ADAPTI"
city: Ekaterinburg
country: Russian Federation
facility: New Hospital Medical Union
city: Gatchina
country: Russian Federation
facility: Municipal Healthcare Institution
city: Kemerovo
country: Russian Federation
facility: Municipal Healthcare Institution
city: Kemerovo
country: Russian Federation
facility: Non-State Healthcare Institution
city: Krasnoyarsk
country: Russian Federation
facility: Krasnoyarsk Medical Academy
city: Moscow
country: Russian Federation
facility: State Healthcare Intstitution of Moscow
city: Nizhniy Novgorod
country: Russian Federation
facility: City Clinical Hospital №12
city: Novosibirsk
country: Russian Federation
facility: Municipal Healthcare Institution
city: Novosibirsk
country: Russian Federation
facility: Regional State Healthcare Institution
city: Perm
country: Russian Federation
facility: Municipal Healthcare Institution
city: Saint-Petersburg
country: Russian Federation
facility: St.Petersburg State Healthcare Institution
city: Saint-Petersburg
country: Russian Federation
facility: St.Petersburg State Healthcare Institution
city: Saint-Petersburg
country: Russian Federation
facility: Saint-Petersburg State Healthcare Institution
city: Saint-Petersburg
country: Russian Federation
facility: St.Petersburg State Healthcare Institution
city: Samara
country: Russian Federation
facility: State Healthcare Institution
city: Saratov
country: Russian Federation
facility: Saratov State Medical University
city: Saratov
country: Russian Federation
facility: Federal State Institution
city: St-Petersburg
country: Russian Federation
facility: State Healthcare Institution
city: St-Petersburg
country: Russian Federation
facility: St.Petersburg State Healthcare Institution
city: St.Petersburg
country: Russian Federation
facility: State Educational Institution for Further Professional Training
city: St.Petersburg
country: Russian Federation
facility: Federal State Healthcare Institution
city: Tomsk
country: Russian Federation
facility: State Institution Research Cardiology Institute
city: Tyumen
country: Russian Federation
facility: Tyumen Cardiology Center,
city: Kharkiv
country: Ukraine
facility: Municipal Clinical Hospital No. 27
city: Kharkiv
country: Ukraine
facility: Department of Cardiology of Central Clinical Hospital
city: Kharkiv
country: Ukraine
facility: L.T. Malaya Institute of Therapy of AMS of Ukraine
city: Kharkiv
country: Ukraine
facility: Kharkiv Medical Academy of Post-Graduate Education
city: Kyiv
country: Ukraine
facility: Kyiv City Clinical Hospital #1
city: Kyiv
country: Ukraine
facility: National Scientific Center
city: Lviv
country: Ukraine
facility: Lviv Danylo Halytsky National University
city: Lviv
country: Ukraine
facility: Lviv Regional State Clinical Treatment and Diagnostics Cardiology Center
city: Uzhgorod
country: Ukraine
facility: Uzhgorod National University
city: Zaporizhzhya
country: Ukraine
facility: Zaporizhzhya Regional Cardiological Dispensary
city: Zhytomyr
country: Ukraine
facility: Zhytomyr city hospital #1
Study officials:
References:
citation: Rosenson RS, Hislop C, Elliott M, Stasiv Y, Goulder M, Waters D. Effects of varespladib methyl on biomarkers and major cardiovascular events in acute coronary syndrome patients. J Am Coll Cardiol. 2010 Sep 28;56(14):1079-88. doi: 10.1016/j.jacc.2010.06.015.