Networked Drug REpurposing for Mechanism-based neuroPrOtection in Acute Ischaemic STROKE
REPO-STROKE II
2 other identifiers
interventional
28
1 country
1
Brief Summary
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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Sep 2022
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 23, 2022
CompletedStudy Start
First participant enrolled
September 5, 2022
CompletedFirst Posted
Study publicly available on registry
March 9, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 29, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
April 30, 2024
CompletedOctober 19, 2023
October 1, 2023
1.5 years
August 23, 2022
October 18, 2023
Conditions
Outcome Measures
Primary Outcomes (1)
SICH as per ECASS III
Frequency of symptomatic intracranial hemorrhages as per ECASS III
30 days
Secondary Outcomes (13)
SICH as per Heidelberg Bleeding Classification
30 days
SICH as per SITSMOST
30 days
SICH as per NINDS
30 days
Mortality
30 days
SAE
30 days
- +8 more secondary outcomes
Study Arms (2)
Riociguat +Propylthiouracil +Perphenazine
EXPERIMENTALTriple combination therapy group: ○ each patient in this group will receive two doses (8 +/- 2 hours between doses) of orally administered combination therapy of riociguat, propylthiouracil, and perphenazine, in addition to standard of care.
standard of care
NO INTERVENTIONControl group: each patient in this group will receive only standard of care
Interventions
Riociguat is an sGC stimulator currently approved and marketed for pulmonary arterial hypertension.
Propylthiouracil, already marketed for the treatment of various subtypes of hyperthyroidism, has been identified as a new member of the class of potent and effective neuronal nitric oxide synthase (NOS1) inhibitors
Perphenazine, already marketed as an antiemetic and antipsychotic drug, presents the best NADPH oxidase (NOX) inhibitory characteristics compared to other compounds of the same drug class.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University Hospital Essen, Department of Neurology
Essen, 45147, Germany
Related Publications (1)
Casas AI, Nogales C, Szepanowski RD, Elbatreek MH, Anastasi E, Sadegh S, Skelton J, Frank B, Wipat A, Baumbach J, Kleinschnitz C, Schmidt HHHW. Synergistic Network Pharmacology: Preclinical Validation and Clinical Safety in Acute Ischemic Stroke. J Am Heart Assoc. 2025 May 20;14(10):e039098. doi: 10.1161/JAHA.124.039098. Epub 2025 May 15.
PMID: 40371623DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Masking Details
- This is a Prospective Randomized Open-label Blinded End-point (PROBE) trial
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 23, 2022
First Posted
March 9, 2023
Study Start
September 5, 2022
Primary Completion
February 29, 2024
Study Completion
April 30, 2024
Last Updated
October 19, 2023
Record last verified: 2023-10
Data Sharing
- IPD Sharing
- Will not share