TTM2
Revolutionising research and care: TTM2’s novel approach for resuscitated cardiac arrest patients
The TTM2 Trial
The TTM2 trial is a phase III, multi-centre, randomized, parallel-group, clinical trial in resuscitated cardiac arrest patients admitted to the intensive care unit to investigate whether targeted temperature management (TTM) to 33°C improves survival and neurological outcome at 6 months compared to a strategy of targeting normothermia and avoiding fever above 37.7°C.
Report:
Primary Outcome: In patients with coma after out-of-hospital cardiac arrest, targeted hypothermia did not lead to a lower incidence of death by 6 months than targeted normothermia.
Case study:
“We need to finish this story by comparing temp management vs. no temp management”
NIKLAS NIELSEN, PRINCIPAL INVESTIGATOR
Background
For patients admitted to the ICU after a cardiac arrest, neurological injury leading to the withdrawal of life support or neurological impairment are the most common outcomes following cardiac arrest.
An out-of-hospital cardiac arrest has an estimated incidence of approximately 1 per 1,000 persons per year (approximately 25,000 individuals in Australia each year).
In studies using detailed instruments, cognitive impairment is reported to be present in 50% of survivors of cardiac arrest discharged from the hospital; this is associated with lower quality of life and increased caregiver strain.
For each resuscitated cardiac arrest patient admitted to ICU who survives to hospital discharge, admission costs alone exceed $120,000. Moreover, the estimated ongoing community-based costs for each patient with moderate cerebral injury is AUD$34,000/year.
Many interventions have been tested in order to lower mortality and improve neurologic function in patients resuscitated after out-of-hospital cardiac arrest. Despite promising results in experimental models, all but one have failed in clinical trials. To date, induced hypothermia is the only intervention that has shown promising results in preliminary clinical trials.
Australian mortality rates for heart attack range between 87-94%.
Trial design
The trial is a multicentre, randomised trial with a 1:1 concealed allocation. Participants will receive either protocolized restrictive administration of non-resuscitation fluids or usual care. The trial will be investigator-initiated and non-commercial. Outcome assessors, participants, statisticians, and conclusion drawers will be blinded to treatment allocation.
Non-resuscitation fluids were defined as fluids other than colloids, blood products and crystalloids at a rate ≥ 5 ml/kg/h. Indication, volume and type of fluid were recorded during the first 5 days after admission. A maximum of 30 patients could be included per centre.
To estimate the potential to reduce the administration of non-resuscitation fluid, a pragmatic "restrictive" protocol for administration of non-resuscitation fluids was devised based on the most restrictive practice already in place for non-resuscitation fluids at any of the participating centres.
The REDUSE Trial opened for recruitment in May 2022 at 8 vanguard sites in Sweden. With 98 patients randomised, enrolments have been paused to allow for a review of methods with a number of improvements scheduled for early 2023.
Key connections
“You hear of working in an agile environment but this really is as agile as it gets.”
Spiral’s contribution
Our Spiral Project Lead and EDC Product Owner for the TTM2 trial is Jess Green
In charge of overseeing software development that’s used in clinical trials, Jess not only engages clients but, like glue, she also pulls the team together along the path of delivery.