Medical management +/- surgery for symptomatic cerebral cavernous malformation: a randomised open pilot trial

<h3>Background</h3> The top uncertainty for people with symptomatic cerebral cavernous malformation (CCM) is whether to have medical management and surgery (with neurosurgery or stereotactic radiosurgery) or medical management alone. <h3>Methods</h3> The CARE pilot trial (ISRCTN41647111) sought 60 people with mental capacity and a symptomatic CCM. Computerised, web-based randomisation assigned participants (1:1) to CCM treatment with medical management and surgery or medical management alone. Assignment was open to investigators, participants, and care givers, but not outcome event adjudicators. The primary outcome was intracranial haemorrhage or new persistent/progressive non-haemorrhagic focal neurological deficit due to CCM or surgery during ≥6 months follow-up. <h3>Results</h3> Investigators screened 511 patients at 28 sites: 322 (63%) eligible, 202 (63%) approached, 96 (48%) uncertain about whether to have surgery for a symptomatic CCM, and 72 participants (median age was 50·6y [38·6-59·2], 41 [57%] female, 66 [92%] white, 56 [78%] had prior ICH, and 28 [39%] had prior epileptic seizure) were randomly assigned to medical management and surgery (n=36; 12 to neurosurgical resection and 24 to stereotactic radiosurgery) or medical management alone (n=36). 67 participants completed follow-up (retention 93%) and adherence was 91%. The primary outcome occurred in 2/33 assigned to medical management and surgery and 2/34 assigned to medical management alone (HR 0·99, 95%CI 0·14-7·03). There were no deaths or SAEs. <h3>Conclusion</h3> This pilot trial exceeded its recruitment target, but a definitive trial will require extensive international engagement.