Effect of Cyclosporine and Remote Ischemic Preconditioning in Reperfusion Ischemia Injury on Tetralogy Fallot Patients With Correction Surgery

Sponsor

Indonesia University (Other)

Overall Status

Completed

CT.gov ID

NCT05691764

Collaborator

(none)

Enrollment

Location

Arms

Actual Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study aimed to evaluate the combined effects of cyclosporine and remote ischemic preconditioning on MDA, calcium cytosol concentration, and mitochondrial edema in tetralogy Fallot patients undergoing corrective surgery.

Condition or Disease	Intervention/Treatment	Phase
Myocardial Injury Cardiac Surgery	Drug: Cyclosporin Procedure: remote ischemic preconditioning Drug: Placebo	N/A

Detailed Description

Forty patients undergoing tetralogy Fallot corrective surgery were randomized to RIPC and cyclosporine (n=20) and control (n=20). Cyclosporin was administered 2 hour pre induction of anesthesia with the dose of 3 mg/kg body weight intravenously. RIPC was performed preoperatively after induction of anesthesia by inflating pressure cuff on the extremity 30 mmHg higher than systolic blood pressure of the patient for 5x5 minutes with 5 minutes reperfusion interval. Blood samples from coronary sinus and biopsies from the myocardial infundibulum were obtained three times at the condition of pre ischemic, ischemic, and reperfusion. MDA was measured from the blood samples, meanwhile calcium cytosol concentration and mitochondrial edema was measured from the biopsy samples.

Study Design

Study Type:

Interventional

Actual Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Effect of Cyclosporine and Remote Ischemic Preconditioning on MDA, Calcium Cytosol Concentration, and Mitochondrial Edema in Reperfusion Ischemia Injury: Research on Tetralogy Fallot Patients With Correction Surgery

Actual Study Start Date :

Sep 1, 2020

Actual Primary Completion Date :

Dec 1, 2021

Actual Study Completion Date :

Sep 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cyclosporin + RIPC This group received cyclosporin intravenously 2 hours pre-induction of anesthesia, with the dose of 3 mg/ kg body weight. RIPC was performed preoperatively after induction of anesthesia by inflating pressure cuff on the extremity 30 mmHg higher than systolic blood pressure of the patient for 5x5 minutes with 5 minutes reperfusion interval.	Drug: Cyclosporin Cyclosporin was administered intravenously with the dose of 3 mg/ kg body weight Other Names: Sandimmun Procedure: remote ischemic preconditioning Performed by inflating pressure cuff on the extremity 30 mmHg higher than systolic blood pressure of the patient for 5x5 minutes with 5 minutes reperfusion interval Other Names: RIPC
Placebo Comparator: Control This group received placebo intravenously 2 hours pre-induction of anesthesia.	Drug: Placebo Intravenous placebo

Arm

Intervention/Treatment

Experimental: Cyclosporin + RIPC

This group received cyclosporin intravenously 2 hours pre-induction of anesthesia, with the dose of 3 mg/ kg body weight. RIPC was performed preoperatively after induction of anesthesia by inflating pressure cuff on the extremity 30 mmHg higher than systolic blood pressure of the patient for 5x5 minutes with 5 minutes reperfusion interval.

Drug: Cyclosporin

Cyclosporin was administered intravenously with the dose of 3 mg/ kg body weight

Other Names:

Sandimmun

Procedure: remote ischemic preconditioning

Performed by inflating pressure cuff on the extremity 30 mmHg higher than systolic blood pressure of the patient for 5x5 minutes with 5 minutes reperfusion interval

Other Names:

RIPC

Placebo Comparator: Control

This group received placebo intravenously 2 hours pre-induction of anesthesia.

Drug: Placebo

Intravenous placebo

Outcome Measures

Primary Outcome Measures

Malondialdehyde (MDA) [1 year]
ROS level is determined by measuring MDA concentration (nmol/mL)
Calcium cytosol concentration [1 year]
Calcium concentration (nmol/mL) in cytosol is determined by ratiometric analysis on Fura Red- dyed heart cells.
Mitochondrial edema [1 year]
Mitochondrial edema (%) is measured by decreasing of optical density that indicates change in mitochondrial matrix volume.

Secondary Outcome Measures

Cardiac index [1 year]
Examined with echocardiography, unit of measurement is litres per minute per square metre (L/min/m2).
Troponin I [1 year]
Measured from venous blood, unit of measurement is nanograms per milliliter (ng/mL).
Creatine kinase- MB (CKMB) [1 year]
Measured from venous blood, unit of measurement is units per liter (IU/L).
Vasoactive inotropic score (VIS) [1 year]
VIS was calculated as: dopamine dose (μg/kg/min) + dobutamine dose (μg/kg/min) + 100 × epinephrine dose (μg/kg/min) + 10 × milrinone dose (μg/kg/min) + 10 000 × vasopressin dose (unit/kg/min) + 100 × norepinephrine dose (μg/kg/min).

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year to 6 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Tetralogy Fallot patient that is undergoing correction surgery
Has an ideal anatomy for corrective surgery, namely: Pulmonary artery size within normal limits (according to the kirklin table), Mc Goon ratio> 1.5, Nakata index> 200, normal coronary artery ostium and good biventricular function.