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

Primary Purpose

Myocardial Injury, Cardiac Surgery

Status
Completed
Phase
Not Applicable
Locations
Indonesia
Study Type
Interventional
Intervention
Cyclosporin
remote ischemic preconditioning
Placebo
Sponsored by
Indonesia University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myocardial Injury focused on measuring RIPC, cyclosporine, ischemia reperfusion injury, MDA, calcium cytosol, tetralogy Fallot, mitochondrial edema, infundibulum

Eligibility Criteria

1 Year - 6 Years (Child)All SexesDoes not accept 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. Exclusion Criteria: Patient refuses the procedure Patient with acute kidney injury Patient without lower extremity Patient with cyclosporin allergy

Sites / Locations

  • Indonesia University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Cyclosporin + RIPC

Control

Arm Description

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.

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Cardiac index
Examined with echocardiography, unit of measurement is litres per minute per square metre (L/min/m2).
Troponin I
Measured from venous blood, unit of measurement is nanograms per milliliter (ng/mL).
Creatine kinase- MB (CKMB)
Measured from venous blood, unit of measurement is units per liter (IU/L).
Vasoactive inotropic score (VIS)
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).

Full Information

First Posted
December 15, 2022
Last Updated
January 10, 2023
Sponsor
Indonesia University
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1. Study Identification

Unique Protocol Identification Number
NCT05691764
Brief Title
Effect of Cyclosporine and Remote Ischemic Preconditioning in Reperfusion Ischemia Injury on Tetralogy Fallot Patients With Correction Surgery
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Completed
Study Start Date
September 1, 2020 (Actual)
Primary Completion Date
December 1, 2021 (Actual)
Study Completion Date
September 1, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Indonesia University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myocardial Injury, Cardiac Surgery
Keywords
RIPC, cyclosporine, ischemia reperfusion injury, MDA, calcium cytosol, tetralogy Fallot, mitochondrial edema, infundibulum

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cyclosporin + RIPC
Arm Type
Experimental
Arm Description
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.
Arm Title
Control
Arm Type
Placebo Comparator
Arm Description
This group received placebo intravenously 2 hours pre-induction of anesthesia.
Intervention Type
Drug
Intervention Name(s)
Cyclosporin
Other Intervention Name(s)
Sandimmun
Intervention Description
Cyclosporin was administered intravenously with the dose of 3 mg/ kg body weight
Intervention Type
Procedure
Intervention Name(s)
remote ischemic preconditioning
Other Intervention Name(s)
RIPC
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Intravenous placebo
Primary Outcome Measure Information:
Title
Malondialdehyde (MDA)
Description
ROS level is determined by measuring MDA concentration (nmol/mL)
Time Frame
1 year
Title
Calcium cytosol concentration
Description
Calcium concentration (nmol/mL) in cytosol is determined by ratiometric analysis on Fura Red- dyed heart cells.
Time Frame
1 year
Title
Mitochondrial edema
Description
Mitochondrial edema (%) is measured by decreasing of optical density that indicates change in mitochondrial matrix volume.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Cardiac index
Description
Examined with echocardiography, unit of measurement is litres per minute per square metre (L/min/m2).
Time Frame
1 year
Title
Troponin I
Description
Measured from venous blood, unit of measurement is nanograms per milliliter (ng/mL).
Time Frame
1 year
Title
Creatine kinase- MB (CKMB)
Description
Measured from venous blood, unit of measurement is units per liter (IU/L).
Time Frame
1 year
Title
Vasoactive inotropic score (VIS)
Description
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).
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
6 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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. Exclusion Criteria: Patient refuses the procedure Patient with acute kidney injury Patient without lower extremity Patient with cyclosporin allergy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jefferson K Hidayat, MD
Organizational Affiliation
Indonesia University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Indonesia University
City
Jakarta
State/Province
DKI Jakarta
ZIP/Postal Code
10430
Country
Indonesia

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
28329231
Citation
Wu Q, Wang T, Chen S, Zhou Q, Li H, Hu N, Feng Y, Dong N, Yao S, Xia Z. Cardiac protective effects of remote ischaemic preconditioning in children undergoing tetralogy of fallot repair surgery: a randomized controlled trial. Eur Heart J. 2018 Mar 21;39(12):1028-1037. doi: 10.1093/eurheartj/ehx030.
Results Reference
result
PubMed Identifier
30621955
Citation
Davidson SM, Ferdinandy P, Andreadou I, Botker HE, Heusch G, Ibanez B, Ovize M, Schulz R, Yellon DM, Hausenloy DJ, Garcia-Dorado D; CARDIOPROTECTION COST Action (CA16225). Multitarget Strategies to Reduce Myocardial Ischemia/Reperfusion Injury: JACC Review Topic of the Week. J Am Coll Cardiol. 2019 Jan 8;73(1):89-99. doi: 10.1016/j.jacc.2018.09.086.
Results Reference
result
PubMed Identifier
25720581
Citation
Zalewski J, Claus P, Bogaert J, Driessche NV, Driesen RB, Galan DT, Sipido KR, Buszman P, Milewski K, Van de Werf F. Cyclosporine A reduces microvascular obstruction and preserves left ventricular function deterioration following myocardial ischemia and reperfusion. Basic Res Cardiol. 2015 Mar;110(2):18. doi: 10.1007/s00395-015-0475-8. Epub 2015 Feb 27.
Results Reference
result
PubMed Identifier
12411407
Citation
Chen HW, Chien CT, Yu SL, Lee YT, Chen WJ. Cyclosporine A regulate oxidative stress-induced apoptosis in cardiomyocytes: mechanisms via ROS generation, iNOS and Hsp70. Br J Pharmacol. 2002 Nov;137(6):771-81. doi: 10.1038/sj.bjp.0704908.
Results Reference
result

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

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