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

NCT05579964 | Completed Phase 2 DMC

• 1 other identifier: LB.02.01/Vll/011/KEP011/2022
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Dexmedetomidine; Myocardial Protection; Tetralogy of Fallot; Total Correction; Double Blind Randomized Controlled Trial; Cardiopulmonary Bypass

Outcome Measures

Primary Outcomes (8)

• Serum Troponin I at baseline

  Troponin I serum concentration will be measured using ELABSCIENCE E-EL-H0649 reagent (ng/mL)

  5 minutes after induction of anesthesia (T1)

• Serum Troponin I at 1 hour after cardiopulmonary bypass

  Troponin I serum concentration will be measured using ELABSCIENCE E-EL-H0649 reagent (ng/mL)

  1 hour after cardiopulmonary bypass (T2)

• Serum Troponin I at 6 hours after cardiopulmonary bypass

  Troponin I serum concentration will be measured using ELABSCIENCE E-EL-H0649 reagent (ng/mL)

  6 hours after cardiopulmonary bypass (T3)

• Serum Troponin I at 24 hours after cardiopulmonary bypass

  Troponin I serum concentration will be measured using ELABSCIENCE E-EL-H0649 reagent (ng/mL)

  24 hours after cardiopulmonary bypass (T4)

• Serum IL-6 at baseline

  IL-6 serum concentration will measured using RnD Quantikine D6050 IL-6 reagent (pg/mL)

  5 minutes after induction of anesthesia (T1)

• Serum IL-6 at 1 hour after cardiopulmonary bypass

  IL-6 serum concentration will measured using RnD Quantikine D6050 IL-6 reagent (pg/mL)

  1 hour after cardiopulmonary bypass (T2)

• Serum IL-6 at 6 hours after cardiopulmonary bypass

  IL-6 serum concentration will measured using RnD Quantikine D6050 IL-6 reagent (pg/mL)

  6 hours after cardiopulmonary bypass (T3)

• Serum IL-6 at 24 hours after cardiopulmonary bypass

  IL-6 serum concentration will measured using RnD Quantikine D6050 IL-6 reagent (pg/mL)

  24 hours after cardiopulmonary bypass (T4)

Secondary Outcomes (8)

• Cardiac output

  5 minutes after induction of anesthesia (T1), 6 hours (T3), 24 hours (T4), and 48 hours (T5) after cardiopulmonary bypass

• Cardiac Index

  5 minutes after induction of anesthesia (T1), 6 hours (T3), 24 hours (T4), and 48 hours (T5) after cardiopulmonary bypass

• Systemic Vascular Resistance (SVR)

  5 minutes after induction of anesthesia (T1), 6 hours (T3), 24 hours (T4), and 48 hours (T5) after cardiopulmonary bypass

• Serum Lactate

  5 minutes after anesthesia induction (T1), and then 1 hour (T2), 6 hours (T3), and 24 hours (T4) after cardiopulmonary bypass

• VIS Score

  1 hour (T2), 6 hours (T3), 24 hours (T4) after cardiopulmonary bypass

Study Arms (2)

DEX Group

EXPERIMENTAL

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

Drug: Dexmedetomidine Hcl 100 Mcg/mL Inj

Control Group

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Dexmedetomidine Hcl 100 Mcg/mL Inj 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

Also known as: Precedex, Kabimidine

DEX Group

Placebo 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

Also known as: NaCl 0.9%

Control Group

Eligibility Criteria

• Age: 1 Month - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cardiovascular Center Harapan Kita Hospital Indonesia: lead

Study Sites (1)

National Cardiovascular Center Harapan Kita Hospital Indonesia

Jakarta, 11420, Indonesia

Location

MeSH Terms

Conditions

Tetralogy of Fallot

Interventions

Dexmedetomidine; Sodium Chloride

Condition Hierarchy (Ancestors)

Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Dian Kesumarini, MD

  National Cardiovascular Center Harapan Kita Hospital Indonesia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Principal Investigator

Study Record Dates

• First Submitted: October 11, 2022
• First Posted: October 14, 2022
• Study Start: October 10, 2022
• Primary Completion: April 10, 2023
• Study Completion: June 10, 2023
• Last Updated: August 24, 2023

Record last verified: 2023-08

Locations

ID (1)