Trial Outcomes & Findings for Remote Ischemic Conditioning in Patients With Acute Stroke (RESIST) (NCT NCT03481777)

Results Overview

Clinical outcome (modified Rankin Scale) at 3 months in acute stroke patients (target diagnosis) (generalized ordinal logistic regression). The assessment will performed by two independent telephone or face-to-face assessors. the mRS range from 0 to 6, with higher scores representing worse outcome (mRS 0, no symptoms; mRS 6, death) If disagreement occurs the patient will be contacted by a third assessor (face-to-face or telephone) who is blinded to the intervention who will assess the level of dependency. * If disagreement occurs between two telephone assessments - a third, and final, telephone or face-to-face assessment will be made. * If disagreement occurs between one face-to-face assessment and one telephone assessment * the face-to-face will be considered the final assessment * If disagreement occurs between two face-to-face assessments - a third, and final, telephone or face-to-face assessment will be made.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

1500 participants

Primary outcome timeframe

3 months

Results posted on

2025-01-27

Participant Flow

The RESIST trial is a prehospital stroke trial. Patients are randomzied to remote ischemic conditioning or sham in the ambualnce before their final diagnosis. Patients who have a stroke (ischemic stroke or intracerebral hemorrhage, n= 902) are the target population and treated further according to randomization and outcome assessed as 3 months modified Rankin Scale . Patients with a non stroke diagnosis (n=531) are not treated further and not followed beyond hospital discharge.

Participant milestones

Participant milestones
Measure	Remote Ischemic Condtioning (RIC) Patients with a prehospital stroke suspicion were randomized and treated with either RIC or sham RIC in the ambulance and continued at the stroke center. Patients with a in-hospital diagnosis of acute ischemic stroke or intracerebral hemorrhage were the target group and study population for the primary endpoint (modified Intention to Treat)	Sham Remote Ischemic Conditioning Patients with a prehospital stroke suspicion were randomized and treated with either RIC or sham RIC in the ambulance and continued at the stroke center. Patients with a in-hospital diagnosis of acute ischemic stroke or intracerebral hemorrhage were the target group and study population for the primary endpoint (modified Intention to Treat)
Overall Study STARTED	749	751
Overall Study COMPLETED	436	466
Overall Study NOT COMPLETED	313	285

Reasons for withdrawal

Reasons for withdrawal
Measure	Remote Ischemic Condtioning (RIC) Patients with a prehospital stroke suspicion were randomized and treated with either RIC or sham RIC in the ambulance and continued at the stroke center. Patients with a in-hospital diagnosis of acute ischemic stroke or intracerebral hemorrhage were the target group and study population for the primary endpoint (modified Intention to Treat)	Sham Remote Ischemic Conditioning Patients with a prehospital stroke suspicion were randomized and treated with either RIC or sham RIC in the ambulance and continued at the stroke center. Patients with a in-hospital diagnosis of acute ischemic stroke or intracerebral hemorrhage were the target group and study population for the primary endpoint (modified Intention to Treat)
Overall Study Withdrawal by Subject	36	31
Overall Study Non stroke = non target population	277	254

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Remote Ischemic Conditioning n=436 Participants Remote Ischemic Conditioning (Active)	Sham n=466 Participants Remote Ischemic Conditioning (Sham)	Total n=902 Participants Total of all reporting groups
Age, Continuous	72 years n=436 Participants	73 years n=466 Participants	73 years n=902 Participants
Sex: Female, Male Female	165 Participants n=436 Participants	170 Participants n=466 Participants	335 Participants n=902 Participants
Sex: Female, Male Male	271 Participants n=436 Participants	296 Participants n=466 Participants	567 Participants n=902 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment Denmark	436 participants n=436 Participants	466 participants n=466 Participants	902 participants n=902 Participants
National Institutes of Health Stroke Scale (NIHSS)	5 points on NIHSS n=436 Participants	5 points on NIHSS n=466 Participants	5 points on NIHSS n=902 Participants
Diagnosis Acute ischemic stroke	349 Participants n=436 Participants	388 Participants n=466 Participants	737 Participants n=902 Participants
Diagnosis Intracerebral hemorrhage	87 Participants n=436 Participants	78 Participants n=466 Participants	165 Participants n=902 Participants

PRIMARY outcome

Timeframe: 3 months

Clinical outcome (modified Rankin Scale) at 3 months in acute stroke patients (target diagnosis) (generalized ordinal logistic regression). The assessment will performed by two independent telephone or face-to-face assessors. the mRS range from 0 to 6, with higher scores representing worse outcome (mRS 0, no symptoms; mRS 6, death) If disagreement occurs the patient will be contacted by a third assessor (face-to-face or telephone) who is blinded to the intervention who will assess the level of dependency. * If disagreement occurs between two telephone assessments - a third, and final, telephone or face-to-face assessment will be made. * If disagreement occurs between one face-to-face assessment and one telephone assessment * the face-to-face will be considered the final assessment * If disagreement occurs between two face-to-face assessments - a third, and final, telephone or face-to-face assessment will be made.

Outcome measures

Outcome measures
Measure	Remote Ischemic Conditioning (RIC) n=436 Participants Patients with acute ischemic stroke or intracerbreral hemorrhage treated with Remote Ischemic Conditioning	Sham n=466 Participants Patients with acute ischemic stroke or intracerbreral hemorrhage treated with Sham
Modified Rankin Scale at 3 Months in Acute Stroke (AIS and ICH)	2 units on a scale Interval 1.0 to 3.0	1 units on a scale Interval 1.0 to 3.0

SECONDARY outcome

Timeframe: 24 hours

Population: 24-hour difference in prehospital stroke score

Neurological deficits are documented using Prehospital Stroke Score (PreSS). Prehospital Stroke Score is assessed in the the ambulance and at 24-hour or at discharge (if discharge occurs before 24 hours). The PreSS score consists of the Cincinnati Prehospital Stroke Scale (CPSS) with an additional opportunity to report other neurological symptoms (e.g. ataxia, sensory disturbances and visual field loss), and PASS (Prehospital Acute Stroke Severity Scale). The PreSS score range from 0-6, with 6 representing the most severe neurological deficits.

Outcome measures

Outcome measures
Measure	Remote Ischemic Conditioning (RIC) n=436 Participants Patients with acute ischemic stroke or intracerbreral hemorrhage treated with Remote Ischemic Conditioning	Sham n=466 Participants Patients with acute ischemic stroke or intracerbreral hemorrhage treated with Sham
Difference Neurological Impairment During the First 24 Hours	-1 units on a scale Interval -2.0 to 0.0	-2 units on a scale Interval -2.0 to 0.0

SECONDARY outcome

Timeframe: 3 months

Population: Acute ischemic stroke patients

Clinical outcome (modified Rankin Scale) at 3 months in acute stroke patients (target diagnosis) (generalized ordinal logistic regression). TThe assessment will performed by two independent telephone or face-to-face assessors. the mRS range from 0 to 6, with higher scores representing worse outcome (mRS 0, no symptoms; mRS 6, death) If disagreement occurs the patient will be contacted by a third assessor (face-to-face or telephone) who is blinded to the intervention who will assess the level of dependency. If disagreement occurs between two telephone assessments - a third, and final, telephone or face-to-face assessment will be made. If disagreement occurs between one face-to-face assessment and one telephone assessment the face-to-face will be considered the final assessment If disagreement occurs between two face-to-face assessments - a third, and final, telephone or face-to-face assessment will be made.

Outcome measures

Outcome measures
Measure	Remote Ischemic Conditioning (RIC) n=349 Participants Patients with acute ischemic stroke or intracerbreral hemorrhage treated with Remote Ischemic Conditioning	Sham n=388 Participants Patients with acute ischemic stroke or intracerbreral hemorrhage treated with Sham
Clinical Outcome (Modified Rankin Scale (mRS) at 3 Months in Acute Ischemic Stroke	1 units on a scale Interval 1.0 to 2.0	1 units on a scale Interval 0.0 to 3.0

SECONDARY outcome

Timeframe: 3 months

Population: Patients with acute ischemic stroke who were treated with reperfusion therapies (intravenous thrombolysis and/or trombectomy)

Clinical outcome (modified Rankin Scale) at 3 months inacute ischemic stroke receiving reperfusion therapy (generalized ordinal logistic regression). The assessment will performed by two independent telephone or face-to-face assessors. the mRS range from 0 to 6, with higher scores representing worse outcome (mRS 0, no symptoms; mRS 6, death) If disagreement occurs the patient will be contacted by a third assessor (face-to-face or telephone) who is blinded to the intervention who will assess the level of dependency. If disagreement occurs between two telephone assessments - a third, and final, telephone or face-to-face assessment will be made. If disagreement occurs between one face-to-face assessment and one telephone assessment the face-to-face will be considered the final assessment If disagreement occurs between two face-to-face assessments - a third, and final, telephone or face-to-face assessment will be made.

Outcome measures

Outcome measures
Measure	Remote Ischemic Conditioning (RIC) n=247 Participants Patients with acute ischemic stroke or intracerbreral hemorrhage treated with Remote Ischemic Conditioning	Sham n=274 Participants Patients with acute ischemic stroke or intracerbreral hemorrhage treated with Sham
Clinical Outcome (Modified Rankin Scale (mRS) at 3 Months in Acute Ischemic Stroke Receiving Reperfusion Therapy	1 units on a scale Interval 1.0 to 3.0	1 units on a scale Interval 1.0 to 3.0

SECONDARY outcome

Timeframe: 3 months

Population: Patients diagnosed with intracerebral hemorrhage

Clinical outcome (modified Rankin Scale) at 3 months in patients with intracerebral hemorrhage (ICH) (generalized ordinal logistic regression). The assessment will performed by two independent telephone or face-to-face assessors. the mRS range from 0 to 6, with higher scores representing worse outcome (mRS 0, no symptoms; mRS 6, death) If disagreement occurs the patient will be contacted by a third assessor (face-to-face or telephone) who is blinded to the intervention who will assess the level of dependency. If disagreement occurs between two telephone assessments - a third, and final, telephone or face-to-face assessment will be made. If disagreement occurs between one face-to-face assessment and one telephone assessment the face-to-face will be considered the final assessment If disagreement occurs between two face-to-face assessments - a third, and final, telephone or face-to-face assessment will be made.

Outcome measures

Outcome measures
Measure	Remote Ischemic Conditioning (RIC) n=87 Participants Patients with acute ischemic stroke or intracerbreral hemorrhage treated with Remote Ischemic Conditioning	Sham n=78 Participants Patients with acute ischemic stroke or intracerbreral hemorrhage treated with Sham
Clinical Outcome (Modified Rankin Scale (mRS) at 3 Months in Patients With Intracerebral Hemorrhage (ICH)	3 units on a scale Interval 2.0 to 5.0	3 units on a scale Interval 2.0 to 5.0

SECONDARY outcome

Timeframe: 3 months

Difference in proportion of patients with complete remission of symptoms within 24 hours (TIA; both with and without DWI) Diagnosis of TIA is documented in the electronic case report form

Outcome measures

Outcome measures
Measure	Remote Ischemic Conditioning (RIC) n=515 Participants Patients with acute ischemic stroke or intracerbreral hemorrhage treated with Remote Ischemic Conditioning	Sham n=536 Participants Patients with acute ischemic stroke or intracerbreral hemorrhage treated with Sham
Difference in Proportion of Patients With Complete Remission of Symptoms Within 24 Hours (TIA; Both With and Without DWI)	96 Participants	90 Participants

SECONDARY outcome

Timeframe: 3 months

MACCE is defined as: Cardiovascular events (cardiovascular death, myocardial infarction, acute ischemic or hemorrhagic stroke) Cardiovascular death: Death from known cardiovascular cause or sudden death from unknown cause (no identified cause of death in medical history and/or autopsy) Acute myocardial infarction: Admission with a discharge diagnosis of ST-elevation myocardial infarction (STEMI) and non-ST elevation myocardial infarction (NSTEMI) and unstable angina pectoris (UAP) Stroke: Admission with a discharge diagnosis of acute ischemic or hemorrhagic stroke. Evaluation is performed using the Danish National Patient Register (LPR) and the DSR at two time points (6 and 15 months after the inclusion of the last patient). Diagnosis of AIS/TIA, ICH and MI (STEMI, NSTEMI, and UAP) are made according to national clinical practice guidelines.

Outcome measures

Outcome measures
Measure	Remote Ischemic Conditioning (RIC) n=436 Participants Patients with acute ischemic stroke or intracerbreral hemorrhage treated with Remote Ischemic Conditioning	Sham n=466 Participants Patients with acute ischemic stroke or intracerbreral hemorrhage treated with Sham
Major Adverse Cardiac and Cerebral Events (MACCE)	57 Participants	62 Participants

SECONDARY outcome

Timeframe: 24 hours

Population: Target population with acute stroke

Reduction in National Institute of Health Stroke Scale (NIHSS) ≥ 4 (baseline versus 24-Hour NIHSS). NIHSS range from 0 to 42, with higher scores representing worse neurological function.

Outcome measures

Outcome measures
Measure	Remote Ischemic Conditioning (RIC) n=425 Participants Patients with acute ischemic stroke or intracerbreral hemorrhage treated with Remote Ischemic Conditioning	Sham n=451 Participants Patients with acute ischemic stroke or intracerbreral hemorrhage treated with Sham
Early Neurological Improvement in Acute Ischemic Stroke Patients (AIS)	108 Participants	131 Participants

Adverse Events

Remote Ischemic Conditioning (RIC)

Serious events: 335 serious events

Other events: 54 other events

Deaths: 41 deaths

Sham

Serious events: 325 serious events

Other events: 11 other events

Deaths: 47 deaths

Serious adverse events

Serious adverse events
Measure	Remote Ischemic Conditioning (RIC) n=713 participants at risk Patients with acute ischemic stroke or intracerbreral hemorrhage treated with Remote Ischemic Conditioning	Sham n=720 participants at risk Patients with acute ischemic stroke or intracerbreral hemorrhage treated with Sham
Cardiac disorders SAE	47.0% 335/713 • Number of events 335 • 90 days Adverse events and adverse device events are defined according to ISO 14155:2011 and European Commission guideline on medical devices (MEDDEV 2.7/3 revision 3).	45.1% 325/720 • Number of events 325 • 90 days Adverse events and adverse device events are defined according to ISO 14155:2011 and European Commission guideline on medical devices (MEDDEV 2.7/3 revision 3).

Other adverse events

Other adverse events
Measure	Remote Ischemic Conditioning (RIC) n=713 participants at risk Patients with acute ischemic stroke or intracerbreral hemorrhage treated with Remote Ischemic Conditioning	Sham n=720 participants at risk Patients with acute ischemic stroke or intracerbreral hemorrhage treated with Sham
Musculoskeletal and connective tissue disorders Upper extremity pain during treatment and/or skin petechia	7.6% 54/713 • Number of events 54 • 90 days Adverse events and adverse device events are defined according to ISO 14155:2011 and European Commission guideline on medical devices (MEDDEV 2.7/3 revision 3).	1.5% 11/720 • Number of events 11 • 90 days Adverse events and adverse device events are defined according to ISO 14155:2011 and European Commission guideline on medical devices (MEDDEV 2.7/3 revision 3).

Additional Information

Dr. Rolf Blauenfeldt

Aarhus University Hospital

Phone: 0045 78450000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place