Metformin in Acute Ischemic Stroke

Conditions and Keywords Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study Ischemic stroke Keywords Ischemic stroke, metformin, neuroprotection, randomized controlled trial Study Design Interventional Study Design Primary Purpose

• Treatment: To study the efficacy of oral Metformin in patients of acute ischemic stroke Study Phase
• Phase 3 Interventional Study Model
• Parallel randomised placebo-controlled trial Model Description
• Number of Arms

Patients will be randomised to one of the following arms:

Intervention: will be provided incremental doses of oral Metformin tablets Placebo: will be provided identical placebo tablets

• Masking
• The following will be masked to the treatment arms:

Participant Care Provider Investigator Outcomes Assessor

• Allocation
• Randomized: Participants are assigned to intervention groups by chance
• Enrolment The study will be conducted in four centers and consecutive consenting, and eligible patients will be enrolled into the study. A screening log will be maintained separately.

Arms, Groups, and Interventions Arm Information

• Arm Title Metformin
• Arm Type
• Experimental
• Arm Description Oral metformin hydrochloride, 250 mg twice daily on Days 0-2, 500 mg twice daily Days 3-5, 750 mg twice daily Days 6-8, and 1000 mg twice daily from Day 9 to Day 90 (maximum dose), titrated to tolerability, plus standard stroke care.

Interventions

• Intervention Type
• Drug: Oral Metformin
• Intervention Description Oral metformin hydrochloride immediate-release, 250 mg twice daily on Days 0-2, 500 mg twice daily Days 3-5, 750 mg twice daily Days 6-8, and 1000 mg twice daily from Day 9 to Day 90 (maximum dose), titrated to tolerability, plus standard stroke care.
• Arm Type
• Placebo
• Arm Description Matching placebo tablets identical in appearance, taken on the same escalation schedule and number of tablets for 90 days, plus standard stroke care.

Pre-stroke metformin users (observational cohort) Patients meeting all other eligibility criteria but already taking metformin before stroke onset. Not randomized; followed prospectively to 90 days. Metformin continued or modified per treating physician.

Outcome Measures Primary Outcome Measure Information • Title: Proportion of participants with good functional outcome (mRS 0-1).

• Description: Modified Rankin Scale (range 0 = no symptoms to 6 = death; higher scores indicate worse disability). Good outcome defined as a score of 0 or 1, assessed by a certified assessor blinded to treatment allocation.

• Time Frame:

  90 days Limit: 254 characters. Secondary Outcome Measure Information

  1. Proportion of participants with mRS 0-1 Modified Rankin Scale (range 0 = no symptoms to 6 = death; higher scores indicate worse disability). Good outcome defined as a score of 0 or 1, assessed by a certified assessor blinded to treatment allocation Assessed at 30 (±7) days
  2. All-cause mortality Proportion of participants who died from any cause. Time: 30 days and 90 days

  3. Barthel Index (BI) score and change from baseline Barthel Index of activities of daily living (range 0-100; higher scores indicate greater independence).

     Time: 30 (±7) and 90 (±7) days

  4. Early neurological improvement (ENI) Decrease of ≥4 points in NIHSS score from baseline (NIHSS range 0-42; higher is worse).

     Time: 7 (±2) days

  5. Early neurological deterioration (END) Increase of ≥2 points in NIHSS score from baseline. Time: 7 (±2) days
  6. Serum high-sensitivity C-reactive protein (hsCRP) Concentration (mg/L) and change from baseline (pre-dose) value. Time: 30 (±7) and 90 (±7) days
  7. Serum vitamin B12 Concentration (pg/mL) and change from baseline. Time: 30 (±7) and 90 (±7) days
  8. Serum holotranscobalamin (holoTC) Concentration (pmol/L) and change from baseline. Time: 30 (±7) and 90 (±7) days

  9. Incidence of adverse events (AEs) Number and proportion of participants with any AE, graded by CTCAE v5.0 severity and causality.

     Randomization to 90 (±7) days

  10. Incidence of serious adverse events (SAEs) Number and proportion of participants with any SAE (per ICH E2A/NDCT Rules 2019 definitions).

      Randomization to 90 (±7) days

  11. Tolerability of study drug Proportion of participants reaching and maintaining the target dose (1000 mg twice daily); proportion with dose reduction, temporary hold or permanent discontinuation due to AEs.

      Randomization to 90 (±7) days

  12. Glycated haemoglobin (HbA1c) Change in HbA1c (%) from baseline, overall and by diabetes status. 90 (±7) days

      Eligibility Sex/Gender

• Sex Both male and female patients will be included in the study. Age Limits
• Minimum Age 18 years.
• Maximum Age
• N/A (No limit) Contacts, Locations, and Investigator Information Central Contact Person
• First Name: Deepti
• Middle Initial
• Last Name or Official Title: Vibha
• Degree: MD (Medicine), DM (Neurology)
• Phone: +91-11-26594485
• Ext:

• Email: deeptivibha@aiims.edu Overall Study Officials

  1. Dr Deepti Vibha All India Institute of Medical Sciences (coordinating site), New Delhi, Delhi, India 110029 Not yet recruiting
  2. Dr Sucharita Ray Postgraduate Institute of Medical Education and Research Chandigarh, India 160012 Not yet recruiting
  3. Dr Saranya B. Gomathy Jawaharlal Institute of Postgraduate Medical Education and Research Puducherry, India 605006 Not yet recruiting
  4. Dr Anand Kumar Institute of Medical Sciences, Banaras Hindu University Varanasi, Uttar Pradesh, India 221005 Not yet recruiting

IPD Sharing Statement

1. Plan to Share IPD: Yes
2. IPD Sharing Plan Description: De-identified individual participant data underlying the published results, together with the data dictionary, will be deposited in a public repository in accordance with ICMR data-sharing guidelines.
3. Supporting Information: Study Protocol; Statistical Analysis Plan; Informed Consent Form; Clinical Study Report; Analytic Code
4. Time Frame: Beginning 6 months and ending 5 years after publication of the primary results
5. Access Criteria: Researchers providing a methodologically sound proposal approved by the trial steering committee, with a signed data access agreement