Inclusion Criteria- A clinical diagnosis of acute ischemic stroke in the MCA or MCA/ACA territory.
- Pre-morbid mRS 0 - 1.
- A baseline DWI lesion between 82 cm3 and 210 cm3 on MRI.
- Patients treated with IV rtPA should meet established criteria for IV rtPA administration in the 0-3 and 3-4.5 hr time periods, respectively.
- The time to the start of infusion of study compound must be ≤ 10 hr after time of symptom onset
- Age ≥18 years and ≤70 years.
- Provision of written informed consent by the patient or from a legally authorized representative according to institutional guidelines and national regulations.
Exclusion Criteria- Evidence from imaging or pre-enrollment investigation of any diagnosis other than acute ischemic stroke likely to cause the presenting symptoms and signs.
- Commitment to decompressive craniectomy (DC) prior to enrollment, or follow-ing enrollment and prior to start of study compound.
- Treatment with IA rtPA or by mechanical means for clot disruption or with hypo-thermia.
- Patients unable to tolerate MRI scanning, e.g. those with pacemakers or automatic defibrillators.
- Pre-morbid mRS ≥ 2.
- Clinical signs of herniation, e.g. one or two dilated, fixed pupils; unconsciousness (i.e., ≥ 2 on item 1a on the NIHSS); loss of other brain stem reflexes attributable to herniation according to the investigator's judgment.
- CT or MRI evidence of hemorrhage or anteroseptal/pineal shift greater ≥2 mm prior to enrollment.
- Rapidly improving symptoms.
- Severe renal disorder from the patient's history (e.g. dialysis) or eGFR of < 30 mL/min/1.73 m2.
- Severe liver disease or ALT, AST, or bilirubin >2 times normal.
- Blood glucose <55 mg/dL at enrollment or immediately prior to administration of RP-1127, or a clinically significant history of hypoglycemia.
- Diagnosis of decompensated heart failure (e.g. clinical diagnosis of pulmonary edema, chest x-ray consistent with heart failure, tachypnea > 20, etc.)
- Sulfonylurea treatment within 30 days.
- Known allergy to sulfa or specific allergy to sulfonylurea drugs.
- Known G6PD enzyme deficiency.
- Pregnancy or breast-feeding. Women must be either post-menopausal (judged by the investigator), permanently sterilized or, if of childbearing age, must have a negative test for pregnancy obtained before enrollment.
- Patients already enrolled in a non-observation-only stroke study, or with life-expectancy <3 months not related to current stroke, or those unlikely to be com-pliant with follow up.
- Patients who, in the opinion of the investigator, are not suitable for the study (rea-son to be documented).