Clinical trial NCT02901379: Effect of 80-mg Atorvastatin on Myocardial Edema
Official title: Effect of 80-mg Atorvastatin on Myocardial Edema Following Coronary Artery Bypass Surgery in Relation With Follistatin-Like Protein-1
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Myocardial Edema
Keywords: atorvastatin
myocardial edema
Follistatin-like 1
FSTL1
atorvastatin 80mg
coronary artery bypass surgery
Lead sponsor: National Cardiovascular Center Harapan Kita Hospital Indonesia
Sponsor class: OTHER
First posted: 2016-09-15
Enrollment: 40
Sex: MALE
Minimum age (years): 40
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to determine whether atorvastatin 80mg can reduce the development of myocardial edema following coronary artery bypass surgery.

This study also want to determine:

1. whether atorvastatin 80mg can influence Follistatin-like 1 (FSTL1) plasma level following bypass surgery?
2. whether there is correlation between myocardial edema and FSTL1 plasma level?
3. the efficacy of atorvastatin 80mg compared to atorvastatin 10mg in reducing hs-CRP (high sensitive-C reactive protein) and MDA (malondialdehyde) plasma level following bypass surgery?
4. the efficacy of atorvastatin 80mg compared to atorvastatin 10mg in raising PKA and PKB plasma level following bypass surgery?

Detailed description: This study is an double blinded experimental study using parallel design. Study subjects are patients in Harapan Kita hospital who are registered to CABG (Coronary Artery Bypass Graft) surgery and fulfill all the eligibility criteria.

The subjects will be first consecutively selected, with male age 40-65 as the criteria. After that the investigators do the randomization with block randomization method. All the subjects will be given drug with label A and label B (only the pharmacist know the which dose of atorvastatin belong to which label).

Total subjects needed for this study are 30 (15 belong to study group and 15 belong to control group) MRI (Magnetic Resonance Imaging) results will be read by two radiologists, and analyzed using cronbach alpha. The results are considered equal if the cronbach \>0,7. If it is proven to be unequal, then the third radiologist will decide.

Statin is known to have several adverse effects, such as myopathy, myositis to rhabdomyolysis, elevated liver enzyme, memory loss, GI (gastrointestinal) disturbance, and severa others. Therefore, the investigators will check baseline CK (creatine kinase) and liver enzyme at the beginning of the study, before the surgery, and if the patient feel any symptoms. Statin will be stopped if patient decide to stop, or if there is increase in ALT (alanine aminotransferase) higher that three time upper normal value, or if there is increase in CK higher than ten times upper normal value.

Statistical analysis using IBM SPSS statistics version 21.0. Comparative analysis for variables such as smoking history, obesity, hypertension, dyslipidemia, diabetes, family history, infarct history, ACE-I/ARB (angiotensin converting enzyme inihibitor /angiotensin receptor blocker) therapy will be using chi-square or fischer. Comparative analysis for variables T2 relaxation time, FSTL1, hs-CRP, PKA (protein kinase A), PKB (Protein Kinase B), MDA, age, CPB (Cardiopulmonary Bypass) time, CABG time will using unpaired t-test or Mann-whitney. Correlative analysis between FSTL1 and T2 relaxation time will be using Pearson test.

Eligibility criteria: Inclusion Criteria:

* Patients with coronary artery disease indicated for CABG surgery
* has signed informed consent

Exclusion Criteria:

* high risk EURO (European System for Cardiac Operative Risk Evaluation) score
* creatinin value\>2 g/dl
* direct bilirubin value \>3 mg/ml
* AST/ALT (aspartate transaminase / alanine transaminase) value \>1,5 times UNL (upper normal limit)
* high pre-operative CKMB (Creatine Kinase-MB) and troponin
* LVEF (Left Ventricular Ejection Fraction) \<45%
* concomitant valve disease required surgery
* contraindicated for MRI
* high degree ventricular arrhytmia
* coagulation disorder
* COPD (chronic obsructive pulmonary disease)
* HIV (Human Immunodeficiency Virus) +, HBV (Hepatitis B Virus)+, HCV (Hepatitis C Virus) +
* conduction abnormality, pacemaker
* electrolyte or blood gas disturbance
* receiving immunosuppressive drug or cytotoxic agent 4 weeks before surgery
* receiving macrolide, azole antifungal, fibrate, or protease inhibitor HIV drug

Primary outcomes:
measure: T2 relaxation time
timeFrame: day 6 after CABG
Secondary outcomes:
measure: FSTL1 plasma level
timeFrame: day 6 after CABG
measure: PKA plasma level
timeFrame: day 6 after CABG
measure: PKB plasma level
timeFrame: day 6 after CABG
measure: hs-CRP plasma level
timeFrame: day 1 after CABG
measure: MDA plasma level
timeFrame: day 1 after CABG
measure: Change from baseline FSTL1 plasma level
timeFrame: day 1 and day 6 after CABG
measure: Change from baseline PKA plasma level
timeFrame: day 1 and day 6 after CABG
measure: Change from baseline PKB plasma level
timeFrame: day 1 and day 6 after CABG
Other outcomes:
Locations:
Study officials:
affiliation: National Cardiovascular Center Harapan Kita
name: Rita Zahara
role: PRINCIPAL_INVESTIGATOR
References: