Latest trial results prompt call to “elevate” intracranial haemorrhage management

Craig Anderson was joined on stage by his INTERACT3 co-investigators at ESOC 2023

Following the presentation of new trials assessing intracranial haemorrhage (ICH) treatment approaches, INTERACT3 and ENRICH, Craig Anderson (The George Institute for Global Health, Sydney, Australia)—who delivered first-time data from the former of the two studies—posited that, “maybe, the time is right to elevate ICH to the same level we see in acute [ischaemic] stroke”, also calling for a “more active approach” to ICH management moving forward.

The recent European Stroke Organisation Conference (ESOC; 24–26 May, Munich, Germany) saw a late-breaking update from the ENRICH study presented by Alex Hall and Jonathan Ratcliff (both Emory University, Atlanta, USA), with the speakers reporting that minimally invasive parafascicular surgery (MIPS; Nico Corporation) was found to be safe, resulted in substantial clot evacuation, and led to functional outcome benefits.

ENRICH compared MIPS to medical management in a total of 300 ICH patients who began treatment within 24 hours of symptom onset across 37 US centres. Its primary endpoint was functional outcome (utility-weighted modified Rankin scale [UW-mRS] score) at six months. Patients were block randomised to receive either MIPS or medical management according to their ICH location—anterior basal ganglia (ABG) or lobar—and Glasgow coma scale (GCS) score. Hall and Ratcliff noted that, following enrolment of 175 patients, the study population was altered to focus only on those with lobar-located ICHs. Complete follow-up data were available in a total of 286 patients.

A primary analysis compared the mean UWmRS at six months between treatment groups, and found higher rates of mRS 0–2 and mRS 0–3 in the surgical cohort. The ENRICH investigators also observed an estimated mean treatment effect of 0.374 with medical management and 0.458 with MIPS (a difference of 0.084). As such, superiority of the intervention—measured via Bayesian posterior probability—was 0.9813, exceeding the prespecified threshold to claim substantial superiority versus medical management (0.975). The ENRICH investigators concluded that the overall benefit of MIPS appears to stem from the “strong positive effect” observed in participants with lobar ICH.

In their presentation, Hall and Ratcliff also reported MIPS as being associated with improved rates of survival, owing to a 9.3% rate of 30-day mortality in the intervention group compared to 18.1% in those who underwent medical management. Finally, they noted that shorter lengths of intensive care unit (ICU) and hospital stays were seen in the intervention group as well.

“This is the first trial to demonstrate functional benefit in surgical clot evacuation among patients with supratentorial ICH,” said Hall, with Ratcliff adding that “the data from this trial will help inform future ICH research and practice”.

These findings drew positive comments from ESOC delegates, with session moderator Else Charlotte Sandset (Oslo University Hospital, Oslo, Norway) saying she is “very optimistic” to see something positive in ICH, before Werner Hacke (University of Heidelberg, Heidelberg, Germany) thanked the researchers and claimed that “we have been waiting for this for decades”.

Late-breaking INTERACT3 data

Immediately after, Anderson took to the podium on behalf of his co-investigators to present the results of INTERACT3—a pragmatic, international, multicentre, blinded-endpoint, stepped-wedge cluster randomised controlled trial conducted at sites spanning nine low- and middle-income countries, and one high-income country. The trial sought to evaluate whether the implementation of a goal-directed ‘care bundle’ incorporating early, intensive lowering of systolic blood pressure, and management algorithms for hyperglycaemia, pyrexia, and abnormal anticoagulation, could improve outcomes in patients with acute spontaneous ICH.

A total of 7,036 patients from 121 hospitals were enrolled in INTERACT3’s modified intention-to-treat population, with 3,221 patients being assigned to the care-bundle group and 3,815 patients assigned to receive ‘usual care’. The care-bundle group demonstrated a significantly lower likelihood of a poor functional outcome, signified by a shift in mRS scores that was also consistent across a range of subgroups and sensitivity analyses, including additional adjustments for country- and patient-related variables, as well as different approaches to multiple imputations for missing data.

In addition, patients in the care-bundle group experienced fewer serious adverse events than those in the usual-care group (16% vs 20%), while lower mortality rates, and health-related quality of life and hospital length-of-stay benefits, were also associated with the intervention. The INTERACT3 investigators found that the number needed to treat (NNT) in order to reduce mortality and provide greater functional benefits versus usual care was just 35.

Concluding his talk, Anderson re-emphasised that intensive blood pressure lowering and other management algorithms for physiological control—administered to all acute ICH patients within several hours of symptom onset—resulted in improved functional outcomes. The speaker also went on to recommend that hospitals should incorporate the approach into clinical practice as part of an active protocol for managing this condition, with a view to enabling a “better standard of care for ICH” globally.

Data from INTERACT3 are now available in The Lancet, while findings from the ENRICH trial were published in Frontiers in Neurology earlier this year.

Jonathan Ratcliff (L) and Alex Hall present ENRICH results at ESOC 2023


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