DESTINY Trial

DESTINY is a phase II/III, 2 arm, multi-centre, patient- and assessor-blinded, parallel-group, individually randomised controlled trial.

To evaluate whether in children undergoing cardiac surgery with cardioplegic arrest, the use of del Nido cardioplegia, compared with St. Thomas’ blood cardioplegia:

• reduces myocardial injury, as determined by AUC for plasma troponin following surgery
• reduces the duration of ischaemia (aortic cross-clamp time), the volume of cardioplegia given, and the need for internal defibrillation during reperfusion
• improves myocardial protection, reducing the frequency or severity of LCOS, and markers of reduced tissue perfusion (arterial lactate and omega)
• improves other clinical outcomes, including duration of mechanical ventilation, length of stay on the Paediatric Intensive Care Unit and in hospital, and 30-day survival
• impacts on changes in the metabolic profile of the myocardium during ischaemia

To determine whether in a UK multi-centre trial of cardioplegia in children, recruitment to time & target, collection of data & biological samples, and adherence to the trial protocol are feasible.

Participants will be recruited from 4 paediatric cardiac surgery centres in the UK: 

• Birmingham Women's and Children’s NHS Foundation Trust
• University Hospitals Bristol and Weston NHS Foundation Trust
• Great Ormond Street Hospital for Children NHS Foundation Trust
• Leeds Teaching Hospitals NHS Trust

220 children aged 0-16 undergoing cardiac surgery

Experimental Arm: del Nido cardioplegia in a 1:4 blood:crystalloid preparation, given at 4-8°C, with an initial dose of 20ml/kg and subsequent doses every 60-90 minutes if required, at the discretion of the surgeon, as required.

 Control Arm: St. Thomas’ Hospital blood cardioplegia in a 4:1 blood:crystalloid using Harefield Hospital preparation (section 7.1), given at 4-8°C, with an initial dose of 20-30ml/kg, subsequent doses of 15 ml/kg every 20-30 minutes at the discretion of the surgeon, as required.

Primary Outcome: Area under the time-concentration curve (AUC) for plasma high-sensitivity troponin-I (μg.h/L) in the first 24 hours after the index aortic cross-clamp release (reperfusion).

 Secondary Outcomes:

• Low cardiac output syndrome (LCOS) defined as either of the following in the first 48 hours after reperfusion: Vasoactive Inotrope Score (VIS) ≥15, or major cardiac event (cardiac arrest, ECLS or death) (n) 
• Duration of mechanical ventilation (hours), defined as the number of hours from termination of index CPB to extubation
• Length of postoperative stay on Paediatric Intensive Care (hours), defined as number of hours from admission to PICU from theatre following index procedure to discharge from PICU
• Max VIS by thresholds: ≥10, ≥15 and ≥20 in the first 48 hours (n)
• Total VIS in the first 4 hours after PICU admission following the index procedure (score)
• Arterial lactate (mmol/L) in the first 12 hours
• Omega, determined by [SaO2]/[SaO2-ScvO2] in the first 12 hours 
• Total aortic cross-clamp time (mins)
• Total volume of cardioplegia given (ml)
• Need for internal defibrillation during reperfusion (n)
• Delayed sternal closure, incidence (n) and duration (days)
• Unplanned reoperation, including chest re-opening on PICU (n)
• Need for new renal replacement therapy (n)
• Lowest estimated glomerular filtration rate (eGFR), calculated using the bedside Schwartz equation and the peak postoperative creatinine on routine monitoring during the first 7 days following the index procedure (ml/min/1.73m2), and according to the paediatric RIFLE categories (n) 
• Length of postoperative stay in the hospital (days), defined as number of days from day of surgery to discharge from hospital or death, whichever is sooner

 

The first Destiny trial participant was randomised on 11 February 2022 in Bristol.

The graph below shows the cumulative number of patients recruited up to 30 April 2023.

 

DESTINY trial is centrally managed and coordinated by the Birmingham Clinical Trials Unit (BCTU) which is part of the University of Birmingham and has a long-term track record in designing, managing and analysing clinical studies.

The study is led by the Chief Investigator, Mr Nigel Drury, Consultant in Paediatric Cardiac Surgery at Birmingham Women’s and Children’s NHS Foundation Trust, and Institute of Cardiovascular Sciences, University of Birmingham.

• Funder: British Heart Foundation (BHF) (funding ref: BHF/CS/20/3/34738)
• Sponsor: University of Birmingham (UoB) (Ref: RG_19-149)
• Research Ethics Committee (REC): West Midlands - Coventry & Warwickshire Research Ethics Committee (Ref: 21/WM/0149)
• Medicines & healthcare products Regulatory Agency (MHRA) (Ref: 21761/0367/001-0001)