Networked Drug REpurposing for Mechanism-based neuroPrOtection in Acute Ischaemic STROKE

A combination therapy proposed to be evaluated in this trial, consisting of three already registered compounds with a validated disease mechanism and with known safety profiles, targets key proteins in the dysregulated signal network in stroke, and is expected to synergistically result in post-stroke blood-brain barrier stabilization and neuroprotection. The synergistic mode of action will allow for low doses and is expected to reduce possible side effects while maintaining maximal efficacy

Inclusion criteria:Informed consent has to be obtained from the patient or a legal representative. In case this is not feasible due to the emergency situation, an alternative informed consent procedure is allowed, according to the current legislation in Germany, as described in section 15.4 and 15.5 of this protocol.Male or female adult, ≥18 to ≤80 years of age. Patients older than 80 years of age may be enrolled after review of an initial safety data set obtained from younger patients as described in section 7.2.Disabling acute ischemic stroke with an NIHSS score of ≤12 at time of randomization.Treatment with IMP can be initiated within 24 hours after the onset of stroke or after last known normal.Exclusion criteria:Patients receiving intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) for the index event (i.e., the current stroke that led to screening the patient for this trial).Prior inability to walk or to lead an independent life, which is defined as daily need for assistance in performing activities of daily living (ADL).Patients who are delirious, comatose or stuporous (a score of ≥ 2 on item 1.a of the NIHSS).Patients undergoing mechanical thrombectomy or intra-arterial thrombolysis.Detection of hemorrhage on baseline CT.Severe dysphagia with inability to swallow and no indication for nasogastric tube as per opinion of the investigator and thus inability to administer IMP.Systolic blood pressure < 110 mmHg at randomization.Pregnant and breastfeeding patients. Females with childbearing potential must comply with using highly effective methods of contraception as defined in section 9.2.Reported severe ongoing hepatic impairment (Child Pugh C).Reported relevant ongoing renal failure with known GFR <30ml/min.Reported ongoing major depression.Reported ongoing tracheal obstruction.Reported ongoing pulmonary hypertension associated with idiopathic interstitial pneumonias (PHIIP)Reported leucopenia or agranulocytosis.Reported agranulocytosis during previous treatment with thiourea derivatives.Reported hypersensitivity to perphenazine or propylthiouracil or riociguat or any of the other excipients.Participation in another clinical trial within the last four weeks.Reported use of phosphodiesterase (PDE) inhibitors (such as sildenafil, tadalafil, vardenafil) within the last 7 days.Reported use of nitrates or nitric oxide donors (such as amyl nitrite) in any form including recreational drugs called 'poppers' within the last 7 days.Reported use of antithyroid drugs within the last 7 days.