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

NCT05691764 | Completed DMC

• 1 other identifier: IndonesiaUAnes055
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Myocardial Injury; Cardiac Surgery

Keywords

RIPC; cyclosporine; ischemia reperfusion injury; MDA; calcium cytosol; tetralogy Fallot; mitochondrial edema; infundibulum

Outcome Measures

Primary Outcomes (3)

• Malondialdehyde (MDA)

  ROS level is determined by measuring MDA concentration (nmol/mL)

  1 year

• Calcium cytosol concentration

  Calcium concentration (nmol/mL) in cytosol is determined by ratiometric analysis on Fura Red- dyed heart cells.

  1 year

• Mitochondrial edema

  Mitochondrial edema (%) is measured by decreasing of optical density that indicates change in mitochondrial matrix volume.

  1 year

Secondary Outcomes (4)

• Cardiac index

  1 year

• Troponin I

  1 year

• Creatine kinase- MB (CKMB)

  1 year

• Vasoactive inotropic score (VIS)

  1 year

Study Arms (2)

Cyclosporin + RIPC

EXPERIMENTAL

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; Procedure: remote ischemic preconditioning

Control

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Cyclosporin DRUG

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

Also known as: Sandimmun

Cyclosporin + RIPC

remote ischemic preconditioning PROCEDURE

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

Also known as: RIPC

Cyclosporin + RIPC

Placebo DRUG

Intravenous placebo

Control

Eligibility Criteria

• Age: 1 Year - 6 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• Patient refuses the procedure
• Patient with acute kidney injury
• Patient without lower extremity
• Patient with cyclosporin allergy

Sponsors & Collaborators

• Indonesia University: lead

Study Sites (1)

Indonesia University

Jakarta, DKI Jakarta, 10430, Indonesia

Location

Related Publications (4)

• 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.

  PMID: 28329231 RESULT

• 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.

  PMID: 30621955 RESULT

• 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.

  PMID: 25720581 RESULT

• 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.

  PMID: 12411407 RESULT

MeSH Terms

Conditions

Reperfusion Injury; Tetralogy of Fallot

Interventions

Cyclosporine

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Heart Defects, Congenital; Cardiovascular Abnormalities; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Jefferson K Hidayat, MD

  Indonesia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 15, 2022
• First Posted: January 20, 2023
• Study Start: September 1, 2020
• Primary Completion: December 1, 2021
• Study Completion: September 1, 2022
• Last Updated: January 20, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

ID (1)