The Role of Dexmedetomidine as Myocardial Protector in Pediatric Cardiac Surgery Total Correction of Tetralogy of Fallot

NCT ID: NCT05579964

Last Updated: 2023-08-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-10
• Study Completion Date: 2023-06-10

Brief Summary

Congenital heart disease (CHD) is the most common congenital abnormality found in newborns with Tetralogy of Fallot (TOF) being the most common cyanotic CHD. Total correction of TOF was performed using a cardiopulmonary bypass (CPB) machine. However, the use of CPB has a negative effect that causes inflammation and myocardial injury. Myocardial protection in patients undergoing total correction of TOF surgery is more difficult than other cyanotic CHD due to a hypertrophic right ventricular condition. Dexmedetomidine (DEX) is a selective α-2 adrenergic, which has major effects including hypnosis, sedation, and analgesia as well as cardiovascular effects. The sedation is induced by stimulating the α-2 adrenergic receptor in the locus coeruleus (LC) in the pons cerebri. DEX also increases the level of GABA and Galanin and reduces endogenous norepinephrine. The lower level of endogenous norepinephrine decreases the afterload of the ventricles, increases cardiac output, and reduces myocardial injury as a result. Furthermore, the peripheral effects of DEX can reduce myocardial ischemia-reperfusion (MIR) by inhibiting NF-кB pathway activation and reducing the number of pro-inflammatory cytokines released. Thus, the administration of DEX can prevent myocardial necrosis and apoptosis, also reducing reperfusion injury when using CPB machines. Research related to the effectiveness of administering DEX as a myocardial protector in classic TOF patients undergoing elective total correction cardiac surgery in Indonesia is less reported. The aim of this study is to determine the effectiveness of DEX as myocardial protector in classic TOF patients undergoing elective total correction cardiac surgery.

Detailed Description

This study is a double blind randomized controlled trial to determine the effectiveness of DEX during CPB as myocardial protection between DEX group and control group. The study population is classic TOF patients who underwent elective total correction cardiac surgery. This study was approved by the research ethical committee (Institutional Review Board) of the National Cardiovascular Center Harapan Kita Jakarta (NCCHK). Before randomization, participants who are eligible based on inclusion and exclusion criterias will be given informed consent. If the guardians of the participants agree, the participants will be included in this research. Sixty-six pediatric participants with classic TOF undergoing elective total correction will be randomly divided into two groups, DEX group and control group. Dexmedetomidine HCl is provided in the form of a liquid injection (Precedex/Kabimidine 200 mcg/2 ml). For the DEX group, DEX was calculated with a priming dose of 0.5 mcg/kg in a 5 ml syringe mixed in priming fluid and 0.25 mcg/kg/hour DEX infusion diluted in 0.9% NaCl 20 ml in a 20 ml syringe administered to the CPB reservoir with an infusion rate of 10 ml/hour. For the control group, the volume of administration of 0.9% NaCl as priming and 0.9% NaCl infusion was given to the CPB machine with adjusted amount and rate same as the DEX group.

We will measure myocardial injury biomarker plasma levels (Troponin I) and cytokines proinflammatory biomarkers plasma level (IL-6) as the primary outcome of myocardial protection. Serum plasma levels of troponin I and IL-6 will be taken 4 times (T1, 5 minutes after induction as baseline level; T2,1 hour after CPB; T3, 6 hours after CPB, and T4, 24 hours after CPB). Secondary outcomes including hemodynamic profile (cardiac output, cardiac index, and systemic vascular resistance, at 5 minute before induction as baseline level, 6 hours, 24 hours, and 48 hours after CPB), serum lactate levels at 5 minutes after induction as baseline level, 1 hour, 6 hours, and 24 hours after CPB, morbidity outcomes (vasoinotropic score at 1 hour, 6 hours, and 24 hours after CPB, length of ventilator use, and length of stay in intensive care).

Conditions

Congenital Heart Disease in Children; Cardiopulmonary Bypass; Tetralogy of Fallot

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

DEX Group

Priming Dexmedetomidine 0.5 mcg/kg, Infusion Dexmedetomidine 0.25 mcg/kg/hour

Group Type: EXPERIMENTAL

Dexmedetomidine Hcl 100 Mcg/mL Inj

Intervention Type: DRUG

Priming dose of 0.5 mcg/kg in a 5 ml syringe mixed in priming fluid and 0.25 mcg/kg/hour DEX infusion diluted in 0.9% NaCl 20 ml in a 20 ml syringe administered to the CPB reservoir with an infusion rate of 10 ml/hour

Control Group

NaCl 0.9% with adjusted amount and rate same as the DEX group

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Priming dose of NaCl 0.9% in a 5 ml syringe mixed in priming fluid and NaCl 0.9% 20 ml in a 20 ml syringe administered to the CPB reservoir with an infusion rate of 10 ml/hour

Interventions

Dexmedetomidine Hcl 100 Mcg/mL Inj

Priming dose of 0.5 mcg/kg in a 5 ml syringe mixed in priming fluid and 0.25 mcg/kg/hour DEX infusion diluted in 0.9% NaCl 20 ml in a 20 ml syringe administered to the CPB reservoir with an infusion rate of 10 ml/hour

Intervention Type: DRUG

Placebo

Priming dose of NaCl 0.9% in a 5 ml syringe mixed in priming fluid and NaCl 0.9% 20 ml in a 20 ml syringe administered to the CPB reservoir with an infusion rate of 10 ml/hour

Intervention Type: DRUG

Other Intervention Names

Precedex; Kabimidine; NaCl 0.9%

Eligibility Criteria

Inclusion Criteria

• The patient's parents or person in charge is willing to participate in the study
• Patients with classic TOF undergoing elective total correction cardiac surgery
• Aged 1 month - 18 years old

Exclusion Criteria

• The patient experiences a change in the surgical plan from elective to immediate or emergency
• Patients with preoperative infection characterized by procalcitonin >0.5ng/mL
• Patients with impaired liver function characterized by an increase in Serum Glutamic Oxaloacetic Transaminase (SGOT)/Serum Glutamic Pyruvic Transaminase (SGPT) more than 1.5 times the upper limit of normal
• Impaired renal function characterized by creatinine > 2 mg/dL
• Patients with coagulation disorders characterized by International Normalized Ratio (INR) > 1.5

Drop-out Criteria:

• Duration of CPB and/or Aortic cross-clamp time exceeding 120 minutes
• Surgery requires more than two attempts of CPB
• Patient fails to wean from CPB
• Patient requires ECMO (Extracorporeal Membrane Oxygenator) postoperatively
• Patients with postoperative reperfusion injury characterized by pulmonary hemorrhage
• Patients with residual lesions in the form of moderate-severe pulmonary stenosis and moderate-severe pulmonary regurgitation.
• Patient dies on the operating table

• Minimum Eligible Age: 1 Month
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cardiovascular Center Harapan Kita Hospital Indonesia

OTHER

Sponsor Role: lead

Responsible Party

Dian Kesumarini

MD, Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Dian Kesumarini, MD

Role: PRINCIPAL_INVESTIGATOR

National Cardiovascular Center Harapan Kita Hospital Indonesia

Locations

National Cardiovascular Center Harapan Kita Hospital Indonesia

Jakarta, , Indonesia

Countries

Indonesia

Other Identifiers

LB.02.01/Vll/011/KEP011/2022

Identifier Type: OTHER

Identifier Source: secondary_id

LB.02.01/Vll/011/KEP011/2022

Identifier Type: -

Identifier Source: org_study_id