AzTrials
AzTrials

Ischemic StrokePhase 1/2GAMES-PILOTNCT01268683

Glyburide Advantage in Malignant Edema and Stroke Pilot

A Phase 1/2 study testing Glyburide for Injection in people with Ischemic Stroke, run by Remedy Pharmaceuticals, Inc. at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The primary objective of this study is to assess the feasibility of enrolling, evaluating, and treating with glyburide for injection severe anterior circulation ischemic stroke participants, whether or not treated with standard of care intravenous (IV) recombinant tissue plasminogen activator (rtPA). Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Ischemic Stroke
What is being tested?
Glyburide for Injection
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
4 sitesUnited States
Study dates
26 May 2011to 7 Jun 2012
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 19Show fewer
  • 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 (reason to be documented).
  • NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • University of Maryland Medical Center

    Baltimore, Maryland

  • Massachusetts General Hospital

    Boston, Massachusetts

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15213

Other trials in United States

About this study

Official title: A Multi-Center, Prospective, Open Label, Phase IIa Trial of RP-1127 (Glyburide for Injection) in Patients With a Severe Anterior Circulation Ischemic Stroke Who Are Likely to Experience Clinically Significant Brain Swelling.

The primary objective of this study is to assess the feasibility of enrolling, evaluating, and treating with glyburide for injection severe anterior circulation ischemic stroke participants, whether or not treated with standard of care intravenous (IV) recombinant tissue plasminogen activator (rtPA). Participants must be between 18-80 years of age, must have a baseline diffusion weighted image (DWI) lesion volume 82 -210 centimeters cubed (cm3), and time from symptom onset to start of study infusion must be ≤10 hour(hr). The secondary objectives are to assess the initial safety and tolerability, and pharmacokinetics (PK) /pharmacodynamics (PD) of glyburide in severe stroke participants, as well as to compare the clinical and magnetic resonance imaging (MRI) outcome data to benchmark data derived from published literature.

Read the detailed description

This is a multi-center, prospective, open label, phase IIa trial of glyburide for injection in 10 participants with a severe anterior circulation ischemic stroke who are likely to experience clinically significant brain swelling.

Participants will receive glyburide, delivered as an IV bolus followed by an IV infusion for 72 hours.

Participants will have a baseline (pretreatment) MRI scan as standard of care, and three follow up MRI scans (at 24+12 hours, 48+12 hours, and 72±12 hours). Since recanalization may have an effect on outcome, the results of vascular studies, obtained as part of standard of care and defined as CTA, MRA or catheter angiography of the head and neck, will be recorded. Additionally, clinical endpoints such as the National Institutes of Health Stroke Scale (NIHSS), Glasgow Coma Scale (GCS) and Full Outline of UnResponsiveness Score (FOUR) Score (baseline, 24±12 hour, 48±12 hour, 72±12 hour and 7±1 days) and Modified Rankin Scale (mRS) (30±5 days and 90±7 days) will be assessed. Safety parameters will be assessed through Day 7 or discharge (whichever is sooner), and then again at Day 30±5 and Day 90±7.

Study participation is expected to last 90±7 days.

Conditions
Ischemic Stroke
Being tested
Glyburide for Injection
Medical subject headings
Ischemic Stroke

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Glyburide for InjectionDrug

    Also called RP-1127, glibenclamide, glybenclamide

    Administered as specified in the treatment arm.

Study groups in NCT01268683
Study groupRoleWhat they receive
Glyburide for InjectionExperimentalThis arm is administered a glyburide bolus followed by continuous infusion of glyburide for 72 hours
Receives: Drug: Glyburide for Injection

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Rate of Enrollment

    The number of months to enroll 10 participants.

    Measured: Day 1

  2. Percentage of Enrolled Participants to Screened Participants

    Measured: Day 1

  3. Percentage of Participants Completing 90-Day Follow-Up

    Measured: Day 90

  4. Percentage of Dose Reductions/ Dose Suspensions

    Measured: Up to Day 3

  5. Percentage of Participants With All Four MRI Assessments Per Protocol

    Measured: Up to Day 3

  6. Number of MRI Assessments Per Participant

    Measured: Up to Day 3

  7. Percentage of Participants Requiring One or More Hypoglycemia Treatments

    Measured: Up to Day 4

  8. Percentage of Participants With Pre-specified Adverse Events Associated With Glyburide According to Protocol

    Measured: Up to Day 4

Secondary outcomes (12)

  1. Number of Participants With Adverse Events and Serious Adverse Events

    Adverse Events (AE's) of special interest (cardiac events, difficulty controlling blood sugar, liver problems, and blood disorders, including anemia) will be followed for 30 days and all Severe Adverse Events (SAE's) will be followed for 90 days. SAE's and AE's were reviewed, and the number of participants with unanticipated adverse events, or drug-related SAE's were assessed.

    Measured: Up to Day 90

  2. Infarcted Hemisphere Volume

    Measured: Baseline, Day 1, Day 2, and Day 3

  3. Absolute Diffusion Weighted Imaging (DWI) Lesion Volume

    Measured: Baseline, Day 1, Day 2, and Day 3

  4. Change From Baseline in DWI Lesion Volume

    Measured: Baseline, Day 1, Day 2, and Day 3 (Day 3 reported)

  5. Midline Shift

    Measured: Baseline, Day 1, Day 2, and Day 3

  6. Ipsilateral Ventricle Volume

    Measured: Baseline, Day 1, Day 2, and Day 3

  7. Frequency of Hemorrhagic Events

    Measured: Day 1, Day 2, and Day 3

  8. National Institute of Health Stroke Scale (NIHSS) Score

    The NIHSS is composed of 11 categories, each of which is scored between 0 and 4. A score of 0 indicates normal function, a higher score indicates more impairment. Category scores are summed to generate the total NIHSS score (possibles scores range from 0-42).

    Measured: Baseline, Day 1, Day 2, Day 3, and Day 7

  9. Glasgow Coma Scale (GCS) Score

    The GCS is scored on a scale between 3 and 15 (3 = the worst, and 15 = best). It is composed of three parameters : Best Eye Response (scored on a scale of 1-4), Best Verbal Response (scored on a scale of 1-5), Best Motor Response (scored on a scale of 1-6)

    Measured: Baseline, Day 1, Day 2, Day 3, and Day 7

  10. Full Outline of UnResponsiveness (FOUR) Score

    The FOUR Score is a 17-point scale (with potential scores ranging from 0 - 16). Decreasing FOUR Score is associated with worsening level of consciousness. The FOUR Score assesses four domains of neurological function: eye responses, motor responses, brainstem reflexes, and breathing pattern.

    Measured: Baseline, Day 1, Day 2, Day 3, and Day 7

  11. Number of Participants Requiring Decompressive Craniectomy (DC)

    Measured: Up to Day 90

  12. Number of Participants With a Modified Rankin Scale (mRS) Score ≤ 4

    The mRS scale runs from 0-6, the scoring is as follows: 0 - No symptoms, 1 - No significant disability, 2 - Slight disability, 3 - Moderate disability, 4 - Moderately severe disability, 5 - Severe disability, 6 - Dead

    Measured: Day 30, Day 90

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Dec 2010 (estimated)
  2. Study start26 May 2011
  3. Primary completion7 Jun 2012
  4. Study completion7 Jun 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01268683
Sponsor's protocol ID
RPI 201
Acronym
GAMES-PILOT
Status last verified
Nov 2024
First submitted
29 Dec 2010
Last updated
22 Nov 2024
Data monitoring committee
Yes

Publications

  • Kimberly WT, Battey TW, Pham L, Wu O, Yoo AJ, Furie KL, Singhal AB, Elm JJ, Stern BJ, Sheth KN. Glyburide is associated with attenuated vasogenic edema in stroke patients. Neurocrit Care. 2014 Apr;20(2):193-201. doi: 10.1007/s12028-013-9917-z.

    PubMed 24072459

  • Sheth KN, Kimberly WT, Elm JJ, Kent TA, Yoo AJ, Thomalla G, Campbell B, Donnan GA, Davis SM, Albers GW, Jacobson S, del Zoppo G, Simard JM, Stern BJ, Mandava P. Exploratory analysis of glyburide as a novel therapy for preventing brain swelling. Neurocrit Care. 2014 Aug;21(1):43-51. doi: 10.1007/s12028-014-9970-2.

    PubMed 24671831

  • Sheth KN, Kimberly WT, Elm JJ, Kent TA, Mandava P, Yoo AJ, Thomalla G, Campbell B, Donnan GA, Davis SM, Albers GW, Jacobson S, Simard JM, Stern BJ. Pilot study of intravenous glyburide in patients with a large ischemic stroke. Stroke. 2014 Jan;45(1):281-3. doi: 10.1161/STROKEAHA.113.003352. Epub 2013 Nov 5.

    PubMed 24193798

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Glyburide for Injection in people with Ischemic Stroke, run by Remedy Pharmaceuticals, Inc. at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Jun 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate of Enrollment (time frame: Day 1). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01268683, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in