The Role of Dexmedetomidine As Myocardial Protection In Pediatric Cyanotic Congenital Heart Disease Undergoing Open Cardiac Surgery Using Cardiopulmonary Bypass Machine: A Preliminary Study

NCT05300802 | Completed Phase 2 DMC

• 1 other identifier: LB.02.01/VII/581/KEP058/2021
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Congenital Heart Diseases (CHD) are one of the most common congenital anomalies. Worldwide, 8 to 9 out of 1000 of children are born with a CHD, of which 25 percent of are cyanotic CHD. In Indonesia, the prevalence is 43.200 out of 4.8 million births annually. The morbidity and mortality of cyanotic CHDs in the National Cardiovascular Center Harapan Kita (NCCHK) are higher than acyanotic CHDs. Open-heart surgery using a cardiopulmonary bypass (CPB) machine temporarily takes over the function of the heart and lung during surgery. However, the use of CPB has several negative effects such myocardial injury, systemic inflammation, and reperfusion injury. Preoperative hypoxia in cyanotic CHD tends to be associated with a higher risk of myocardial injury. Myocardial protection has an important role in attenuating those effects. Generally, we use a cardioplegia solution as myocardial protection, but there are several non-cardioplegia techniques that can be used to enhance myocardial protection during cardiac bypass, such as adding an anesthetic agent. Dexmedetomidine (DEX) is the active dextroisomer of medetomidine, 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 proinflammatory cytokines released. Research related to the priming and infusion of DEX during CPB in patients with cyanotic CHDs who are undergoing open-heart surgery is less reported. The aims of this study are to determine the effectiveness of the priming and infusion of DEX during CPB as myocardial protection by using two different doses compared to the control group. The population included in this study is pediatric patients with cyanotic CHD who are undergoing open-heart surgery using CPB and who classified as 6 to 9 in the Aristotle Score.

Conditions

Congenital Heart Disease in Children; Cardiopulmonary Bypass

Keywords

Dexmedetomidine; Myocardial Protection; Pediatric Cyanotic Congenital Heart Disease; Cardiopulmonary Bypass; Aristotle Score

Outcome Measures

Primary Outcomes (8)

• Serum Troponin I at baseline

  Troponin I serum concentration will be measured using RnD Quantikine 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 RnD Quantikine 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 RnD Quantikine 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 RnD Quantikine reagent (ng/mL)

  24 hours after cardiopulmonary bypass (T4)

• Serum IL-6 at baseline

  IL-6 serum concentration will measured using an Elecsys 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 an Elecsys 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 an Elecsys 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 an Elecsys IL-6 reagent (pg/mL)

  24 hours after cardiopulmonary bypass (T4)

Secondary Outcomes (8)

• Cardiac output

  6 hours (T3), 24 hours (T4), and 48 hours (T5) after cardiopulmonary bypass

• Cardiac Index

  6 hours (T3), 24 hours (T4), and 48 hours (T5) after cardiopulmonary bypass

• Systemic Vascular Resistance (SVR)

  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

  6 hours (T3), 24 hours (T4), and 48 hours (T5) after cardiopulmonary bypass

Study Arms (3)

Group A

PLACEBO COMPARATOR

Ringer acetate

Drug: Placebo

Group B

EXPERIMENTAL

Priming Dexmedetomidine 1 mcg/kg, Intravenous Ringer acetate

Drug: Dexmedetomidine Hcl 100 Mcg/mL Inj

Group C

EXPERIMENTAL

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

Drug: Dexmedetomidine Hcl 100 Mcg/mL Inj

Interventions

Placebo DRUG

50 ml of Ringer acetate will be added to the priming solution and followed by a continuous 50 ml infusion of Ringer acetate running at 25 ml/hour.

Also known as: Ringer Acetate

Group A

Dexmedetomidine Hcl 100 Mcg/mL Inj DRUG

1 mcg/kg diluted DEX will be added to the priming solution and followed by a continuous infusion of 50 ml Ringer acetate running at 25 ml/hour.

Also known as: Kabimidine

Group B

Eligibility Criteria

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

You may qualify if:

• All the patients guardian consent to participate in this study
• Patient with Cyanotic CHD who are undergoing open-heart surgery using CPB with an Aristotle score of 6-9
• Patient is aged between 1 month to 6 years

You may not qualify if:

• Elective surgery patients who change into an emergency case surgery
• Patient with procalcitonin levels exceeding 0.5 ng/ml with the symptoms of infection
• Patient with liver dysfunction as measured by an increase of Glutamic Oxaloacetic Transaminase (SGOT)/ Serum Glutamic Pyruvic Transaminase (SGPT) levels more than 1.5 times from baseline
• Patient with Renal dysfunction as measured by creatinine levels exceeding 2 mg/dL
• Drop out Criteria:
• Duration of CPB and/or Aortic cross-clamp time exceeding 120 minutes
• Intraoperative anatomy of CHDs finding is different from the preoperative diagnosis so that the patient no longer fulfils the Aristotle score of 6-9
• Surgery requires more than two attempts of CPB
• Patient fails to wean from CPB
• Patient requires ECMO (Extracorporeal Membrane Oxygenator) postoperatively
• 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

Interventions

Dexmedetomidine

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

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: December 20, 2021
• First Posted: March 29, 2022
• Study Start: December 16, 2021
• Primary Completion: May 16, 2022
• Study Completion: July 16, 2022
• Last Updated: September 28, 2022

Record last verified: 2022-09

Locations

ID (1)