Nitric Oxide During Bypass for Arterial Switch Operation

Brief Title

Nitric Oxide During Bypass for Arterial Switch Operation

Official Title

A Randomised Controlled Trial of Nitric Oxide Administration During Cardiopulmonary Bypass in Infants Undergoing Arterial Switch Operation for Repair of Transposition of the Great Arteries

Brief Summary

      This trial will test if adding nitric oxide (NO) gas to the cardiopulmonary bypass (CPB)
      circuit in infants undergoing an arterial switch operation (ASO) for Transposition of the
      Great Arteries (TGA) changes the incidence of major postoperative adverse events (AEs).

      Major postoperative AEs include cardiac arrest, emergency chest opening, use of ECMO (machine
      that acts as an artificial heart and lung during surgery), and death.

      Participants will be randomised to receive oxygen plus nitric oxide (intervention arm) or
      oxygen without nitric oxide (control arm) during CPB.
    

Detailed Description

      The incidence of congenital heart disease (CHD) is approximately 1/100 live born children, of
      which up to 50% require cardiac surgery to correct the underlying abnormality at some stage
      during their life. (Centre for Disease Control and Prevention, USA). Despite major
      improvements in CPB devices, the exposure of host blood to large artificial organ surfaces,
      combined with myocardial injury during planned myocardial ischemia, results in a significant
      systemic inflammatory response. CPB-triggered systemic inflammatory syndrome is responsible
      for the most serious and potentially life-threatening side effects associated with cardiac
      surgery. It is characterized by endotoxin release, leukocyte and complement activation, and
      widespread activation of inflammatory mediators, resulting in endothelial leak, increased
      oxygen consumption, and organ dysfunction.

      NO is an endogenous anti-inflammatory mediator that helps to protect endothelial beds and
      immunologically active cells. NO has a myocardial protective effect by reducing reperfusion
      injury. NO generation is essential for regulation of endothelial function and microvascular
      inflammation. However, dysregulation of endogenous NO during CPB may aggravate the subsequent
      inflammatory response.

      A randomized controlled study adding NO into the bypass circuit was conducted by the Royal
      Children's Hospital in Melbourne on 198 children. This pilot study confirmed the positive
      effects of gaseous NO reported in the U.S. trial, as well as a reduction in the incidence of
      low cardiac output syndrome (LCOS). Other improved patient outcomes included a reduced need
      for extracorporeal life support (ECLS), trends towards a reduced length of stay, and shorter
      duration of ventilation. In light of these promising preliminary results from these two
      separate studies, a large multicentre trial to test these findings in children requiring
      cardiac surgery is needed.

      The NASO study is running concurrently with the Nitric Oxide during Cardio Pulmonary Bypass
      during surgery for congenital heart defects: A Randomised Controlled Trial study (ANZCTR
      Trial Registry ID: ACTRN12617000821392) within Australia (run by Lady Cilento, Brisbane).
      This study is aiming to look at the effects of Nitric Oxide on all children under the age of
      2 years undergoing bypass surgery for CHD.

      TGA presents in 5-7% of all patients with congenital heart disease and isolated TGA is
      managed in a similar manner all over the world. The surgical treatment for this is the ASO.
      Hence this single operation and diagnosis provides an appropriate setting to evaluate the
      efficacy of NO in the CPB circuit. By allowing each centre to have their own protocols of
      care (pre, intra and postoperatively) and only collecting 'routine clinical data", the
      investigators anticipate each centre having high rates of screening and consent.

      Patients will be stratified by centre and by age at time of surgery. Participants will be
      randomized into one of two arms:

        -  Intervention arm will receive NO 20 parts per million (ppm) into the oxygenator of a
           cardio-pulmonary bypass circuit

        -  Control arm will not receive NO

      At the end of CPB, the participants will return to the Intensive Care Unit where normal care
      will continue.

      A total of 800 participants will be enrolled in the study and will be stratified by centre
      and age at time of surgery.

      Study aims to investigate whether exposure to gaseous NO reduces the incidence of
      postoperative major adverse events in infants on cardiopulmonary bypass.
    

Study Phase

Phase 3

Study Type

Interventional

Primary Outcome

Major adverse events

Secondary Outcome

 Length of stay in ICU (hours)

Condition

Low Cardiac Output Syndrome

Intervention

Nitric Oxide

Study Arms / Comparison Groups

 Intervention arm

Description:  • Intervention arm will receive nitric oxide 20 parts per million (ppm) into the oxygenator of a cardio-pulmonary bypass circuit

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

800

Start Date

July 11, 2018

Completion Date

December 31, 2021

Primary Completion Date

December 31, 2021

Eligibility Criteria

        Inclusion criteria;

        Each participant must meet all of the following criteria to be enrolled in this study:

          -  Infant aged greater than or equal to 36 weeks gestation

          -  Infants less than 2 years

          -  Diagnosed with TGA and requiring Arterial Switch Operation

          -  Consent of parents/guardian.

        Exclusion criteria

        Potential participants will be excluded if they meet any of the following criteria:

          -  They have multiple major congenital anomalies (anomalies which affect the infant's
             life expectancy or health status)

          -  They have multiple other cardiac abnormalities (with the exception of ASD, VSD or PDA)

          -  They weigh less than 2.2kgs.

          -  Prior surgical exposure to cardio-pulmonary bypass
      

Gender

All

Ages

N/A - N/A

Accepts Healthy Volunteers

No

Contacts

Warwick Butt, +61 3 93455522, [email protected]

Location Countries

Australia

Location Countries

Australia

NCT ID

NCT03661385

Organization ID

38017

Secondary IDs

ACTRN12618000089235p

Responsible Party

Sponsor-Investigator

Study Sponsor

Warwick Butt

Study Sponsor

Warwick Butt, Principal Investigator, MRCI

Verification Date

August 2020