Combining existing drugs to protect the brain after an ischemic stroke

Networked Drug REpurposing for Mechanism-based neuroPrOtection in Ischaemic STROKE (REPO-STROKE IIa)

This study is testing a new combination of existing medications to see if it can protect the brain and improve recovery for adults who have had a recent stroke.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 28 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Maastricht University (Academic / other)
• Locations: 1 site (Essen)
• Trial ID: NCT05762146 on ClinicalTrials.gov

What this trial studies

This trial evaluates a combination therapy using three already registered compounds that target key proteins involved in the dysregulated signaling network during an acute ischemic stroke. The approach aims to stabilize the blood-brain barrier and provide neuroprotection through a synergistic mechanism, allowing for lower doses and potentially fewer side effects. The study will enroll adult patients who have experienced a disabling acute ischemic stroke and can be treated within 24 hours of symptom onset.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 80 who have experienced a disabling acute ischemic stroke with a specific NIHSS score.

Not a fit: Patients who have received intravenous thrombolysis for their current stroke or those with prior disabilities may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve recovery outcomes for patients suffering from acute ischemic stroke.

How similar studies have performed: While there is a high need for novel neuroprotective therapies in stroke treatment, this specific combination approach is relatively novel and has not been extensively tested in prior studies.

Eligibility criteria

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.

Where this trial is running

Essen

• University Hospital Essen, Department of Neurology — Essen, Germany (Recruiting)

Study contacts

• Study coordinator: Harald Schmidt, MD PhD

Conditions Ischemic Stroke, Acute