## Protocol Section
### Identification Module
**NCT ID:** NCT02901379

**Brief Title:** 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

#### Organization Study ID Info
**ID:** LB.02.01/VII/090/KEP.013/2016
#### Organization
**Class:** OTHER
**Full Name:** National Cardiovascular Center Harapan Kita Hospital Indonesia
### Status Module
#### Completion Date
**Date:** 2018-08

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2018-08-23

**Type:** ACTUAL

**Last Update Submit Date:** 2018-08-22

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2018-08

**Type:** ACTUAL

#### Start Date
**Date:** 2016-10

**Status Verified Date:** 2018-08

#### Study First Post Date
**Date:** 2016-09-15
**Type:** ESTIMATED
**Study First Submit Date:** 2016-09-06
**Study First Submit QC Date:** 2016-09-14
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** National Cardiovascular Center Harapan Kita Hospital Indonesia

#### Responsible Party

**Investigator Affiliation:** National Cardiovascular Center Harapan Kita Hospital Indonesia

**Investigator Full Name:** Rita Zahara

**Investigator Title:** Cardiologist

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Oversight Has DMC:** True

### Description Module

**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.

### Conditions Module

**Conditions:**

- Myocardial Edema

**Keywords:**

- atorvastatin

- myocardial edema

- Follistatin-like 1

- FSTL1

- atorvastatin 80mg

- coronary artery bypass surgery

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** QUADRUPLE

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** PREVENTION

#### Enrollment Info

**Count:** 40

**Type:** ACTUAL

**Phases:**

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Subjects who will receive atorvastatin 80mg for two weeks

**Intervention Names:**

- Drug: Atorvastatin 80mg

**Label:** Atorvastatin 80mg

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Subject who will receive atorvastatin 10mg

**Intervention Names:**

- Drug: Atorvastatin 10mg

**Label:** Atorvastatin 10mg

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Atorvastatin 80mg

**Description:** Subject will be given atorvastatin 80mg for two weeks

**Name:** Atorvastatin 80mg

**Other Names:**

- Lipitor

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Atorvastatin 10mg

**Description:** Subjects will be give atorvastatin 10mg as part of standard therapy in hospital

**Name:** Atorvastatin 10mg

**Other Names:**

- Lipitor

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

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

**Measure:** T2 relaxation time

**Time Frame:** day 6 after CABG

#### Secondary Outcomes

**Description:** FSTL1 plasma level difference between control and study group

**Measure:** FSTL1 plasma level

**Time Frame:** day 6 after CABG

**Description:** PKA plasma level difference between control and study group

**Measure:** PKA plasma level

**Time Frame:** day 6 after CABG

**Description:** PKB plasma level difference between control and study group

**Measure:** PKB plasma level

**Time Frame:** day 6 after CABG

**Description:** hs-CRP plasma level difference between control and study group

**Measure:** hs-CRP plasma level

**Time Frame:** day 1 after CABG

**Description:** MDA plasma level difference between control and study group

**Measure:** MDA plasma level

**Time Frame:** day 1 after CABG

**Measure:** Change from baseline FSTL1 plasma level

**Time Frame:** day 1 and day 6 after CABG

**Measure:** Change from baseline PKA plasma level

**Time Frame:** day 1 and day 6 after CABG

**Measure:** Change from baseline PKB plasma level

**Time Frame:** day 1 and day 6 after CABG

### Eligibility Module

**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

**Maximum Age:** 65 Years

**Minimum Age:** 40 Years

**Sex:** MALE

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Overall Officials

**Official 1:**

**Affiliation:** National Cardiovascular Center Harapan Kita

**Name:** Rita Zahara

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M7657

- Name: Edema

- Relevance: HIGH

- As Found: Edema

### Condition Browse Module - Meshes

- ID: D000004487

- Term: Edema

### Intervention Browse Module - Ancestors

- ID: D000000924

- Term: Anticholesteremic Agents

- ID: D000000960

- Term: Hypolipidemic Agents

- ID: D000000963

- Term: Antimetabolites

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000057847

- Term: Lipid Regulating Agents

- ID: D000019161

- Term: Hydroxymethylglutaryl-CoA Reductase Inhibitors

- ID: D000004791

- Term: Enzyme Inhibitors

### Intervention Browse Module - Browse Branches

- Abbrev: Lipd

- Name: Lipid Regulating Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M351

- Name: Atorvastatin

- Relevance: HIGH

- As Found: Of each

- ID: M4243

- Name: Anticholesteremic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4278

- Name: Hypolipidemic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4281

- Name: Antimetabolites

- Relevance: LOW

- As Found: Unknown

- ID: M28883

- Name: Lipid Regulating Agents

- Relevance: LOW

- As Found: Unknown

- ID: M21155

- Name: Hydroxymethylglutaryl-CoA Reductase Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000069059

- Term: Atorvastatin

### Misc Info Module

- Version Holder: 2024-05-24
