The INTERACT3 study showed that timely administration of a care bundle that included early intensive lowering of systolic blood pressure, strict glucose control, treatment of fever, and rapid reversal of abnormal anticoagulation led to less disability, lower rates of death, and better overall quality of life.
“This is a groundbreaking result. It is the first-ever published trial in ICH patients to show a clear benefit on functional outcomes and on mortality,” lead investigator Craig Anderson, MD, director of global brain health at the George Institute for Global Health, Sydney, said in an interview.
“These results show that, if we can organize care and focus on optimal management of these four aspects of the health of the patient, they do better,” Dr. Anderson said.
‘Game changer’
“This is a game changer because now we have level A evidence showing something is definitely beneficial for these patients,” Dr. Anderson added. “That means hospitals have the imperative to organize their systems to do these things and maximize care. We have never had that before.”
Dr. Anderson noted that, while some previous studies have suggested benefit from various interventions, such as early lowering of blood pressure, the results have not been conclusive.
“This means the intervention has not always been implemented, leading to large variations in clinical practice. But now we have a package that is proven to work; this should become a guideline-recommended practice,” he commented.
The INTERACT-3 results were presented at the European Stroke Organisation conference in Munich. They were also simultaneously published online in The Lancet.
Dr. Anderson explained that, until now, there haven’t been any proven treatments for ICH. “There has been a lot of energy and research put into the field, but this has resulted in several interventions that are ‘probably useful’ or which have a level B recommendation,” he said. “No therapy has been shown to be beneficial in a totally conclusive way, so we are still not entirely sure exactly whether the treatments we use actually make a difference.”
The INTERACT3 researchers therefore decided to evaluate a care package consisting of a bundle of several treatments in the hope that they may have additive or synergistic effects.
The study involved 7,036 patients with imaging-confirmed spontaneous ICH who presented within 6 hours of symptom onset to one of 121 hospitals in 10 mainly low- and middle-income countries: Brazil, China, India, Mexico, Nigeria, Pakistan, Peru, Sri Lanka, Vietnam, and Chile.
Using a cluster design, all hospitals started with usual care as a control and then at some point during the study started using the care bundle intervention.
The care-bundle protocol included the early intensive lowering of systolic blood pressure (target, < 140 mm Hg), strict glucose control (target, 6.1-7.8 mmol/L in those without diabetes and 7.8-10.0 mmol/L in those with diabetes), antipyrexia treatment (target body temperature, ≤ 37.5° C), and rapid reversal of warfarin-related anticoagulation (target international normalized ratio, 1.5) in patients for whom these variables were abnormal.
Overall, the modified intention-to-treat population included 3,221 patients who were assigned to the care-bundle group and 3,815 who were assigned to the usual-care group. Primary outcome data were available for 2,892 patients in the care-bundle group and 3,363 patients in the usual-care group.
The primary outcome was functional recovery, measured with the Modified Rankin Scale at 6 months. Results show that the likelihood of a poor functional outcome was lower in the care-bundle group (common odds ratio, 0.86; P = .015).
Patients who received the interventional care bundle also had a significantly lower rate of serious adverse events (16.0% vs. 20.1%) and mortality (14.1% vs. 17.0%).