CONTRAST : Collaboration for new treatments of acute stroke

Challenges
Intraarterial treatment (IAT) with the use of a retrievable stent improves outcome in selected patients with acute ischemic stroke (AIS) and a proximal intracranial artery occlusion. Still, major challenges in the treatment of acute stroke remain. First, about 15% of all strokes are intracerebral hemorrhages (ICH), for which treatment options are very limited. Second, only few patients with AIS eligible for EVT. And third, even after successful intraarterial treatment, in active treatment arms of recent IAT trials one to two thirds of patients still had a poor outcome.
Incomplete microvascular reperfusion despite recanalization of the occluded artery is a major contributor to poor outcome after AIS. Possible mechanisms are distal microembolization and distal microthrombotic occlusion through activation of platelets and pro-coagulatory pathways and possibly also through microvascular occlusion through cellular swelling by activation of the innate and adaptive arms of the immune system.

Mission
Our mission is to improve the effectiveness and safety of acute treatment for stroke and to increase the number of eligible patients by expanding indications for treatment.

Aims
Our major aim is improve microvascular reperfusion, and thereby improving outcome for our patients. A second, just as important aim is to increase the number of patients who potentially benefit from treatment, by extending the indications for thrombectomy, bringing new treatments into the ambulance, and by testing new treatments for intracerebral hemorrhage.

Consortium
Our consortium is a unique nationwide collaboration of clinical and translational scientists from all academic and large clinical centers who want to act together to improve the treatment of acute stroke.

Randomized clinical trials
We will perform five large acute stroke trials to test novel treatment strategies, aimed at preservation of ischemic tissue and improving outcome by including:

  1. pre-hospital augmentation of collateral blood flow and blood pressure reduction: MR ASAP
  2. antithrombotics to prevent microvascular occlusion after IAT: MR CLEAN MED
  3. immediate IAT without preceding thrombolysis: MR CLEAN NO IV
  4. IAT in the 6 to 24 hour time window: MR CLEAN LATE
  5. microsurgical hematoma evacuation in patients with ICH: DUTCH ICH pilot

Translational research
Apart from providing direct answers to pressing clinical questions, the trials will provide a wealth of prognostic and etiologic information. The trials will have similar designs and data structure. Biomarker information from serial blood samples, neuro-imaging and thrombus material will be gathered and stored centrally.
  1. We aim to identify patients who will benefit from these interventions through advanced imaging;
  2. we will elucidate mechanisms of incomplete microvascular reperfusion with the aim to develop novel stroke treatments in animal models, in combination with data from our clinical biobank, which stores blood, plasma and extracted thrombi;
  3. we apply discrete event modelling (DES) with data from the trials, to optimize stroke care.
On behalf of the CONTRAST consortium,

Diederik Dippel
Charles Majoie