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Effect of 80-mg Atorvastatin on Myocardial Edema

Phase 3
Completed
Conditions
Myocardial Edema
Interventions
Registration Number
NCT02901379
Lead Sponsor
National Cardiovascular Center Harapan Kita Hospital Indonesia
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
40
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Atorvastatin 80mgAtorvastatin 80mgSubjects who will receive atorvastatin 80mg for two weeks
Atorvastatin 10mgAtorvastatin 10mgSubject who will receive atorvastatin 10mg
Primary Outcome Measures
NameTimeMethod
T2 relaxation timeday 6 after CABG

T2 relaxation time (in ms) difference between control and study group

Secondary Outcome Measures
NameTimeMethod
FSTL1 plasma levelday 6 after CABG

FSTL1 plasma level difference between control and study group

PKA plasma levelday 6 after CABG

PKA plasma level difference between control and study group

PKB plasma levelday 6 after CABG

PKB plasma level difference between control and study group

hs-CRP plasma levelday 1 after CABG

hs-CRP plasma level difference between control and study group

MDA plasma levelday 1 after CABG

MDA plasma level difference between control and study group

Change from baseline FSTL1 plasma levelday 1 and day 6 after CABG
Change from baseline PKA plasma levelday 1 and day 6 after CABG
Change from baseline PKB plasma levelday 1 and day 6 after CABG
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