Table 1.
Summary of characteristics of 19 clinical trials and research papers included in this systematic review on remote ischemic per-conditioning application on acute ischemic stroke patients
| NTC Number Acronym/Ref |
Country | Registered year | Estimated enrollment | Age | Criteria | Time before inclusion | Prehospital intervention | Application # cycles Pressure |
Application of RIC | Intervention | Primary outcome measures | Recruitment status |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT0097596 [21] | Denmark | 2009 | 120 | > 18 | Ischemic stroke and rtPA therapy candidate, cerebral infarct showed on MRI | 4.5 h | Yes |
Manual rIPerC, 4 × 5′ Up to 25 mmHg above systolic BP |
Non-affected upper extremity |
One time Control group: not RIC simulation |
Difference in infarct growth (PWI-DWI) after 24 h (Salvage index) | Completed and published |
| France | 2014 | 200 | > 18 | Carotid ischemic stroke, confirmed by MRI, NIHSS ≥5 and ≤ 25 | < 6 h | No |
Device, 4 × 5′ 110 mmHg |
Non-affected lower extremity |
One time after initial MRI Control group: RIC simulation (no pressure) |
Infarct volume by MRI at 24 h mRS at 90 days |
Completed and published | |
| RECAST [17] | UK | 2015a | 26 | > 18 | Ischemic stroke with motor deficits on arm and/or leg | < 24 h | No |
Manual RIC, 4 × 5′ Up to 20 mmHg above systolic BP |
Non-affected upper extremity |
One time Control group: manual RIC simulation (30 mmHg) |
Tolerability and feasibility | Complete and published |
|
REVISE-1 [18] |
China | 2017 | 20 | 18–80 | Ischemic Stroke and endovascular recanalization | < 6 h | No |
Device, 5 × 5′ 200 mmHg |
Both upper extremities |
One time No control group |
Frequency of adverse events at 90 days | Completed |
|
rtPA-RIC1 [19] |
China | 2017 | 30 | > 18 | Confirmed Ischemic Stroke and rtPA therapy on going | < 4.5 h | No |
Doctormate device, 5 × 5′ 200 mmHg |
Both upper extremities |
One time 2 h after rtPA therapy; twice daily for 6 days. Control group: not RIC simulation |
Feasibility of RIC within 7 days | Completed |
|
ReCAST-2 |
UK | 2016 | 120 | > 18 | Ischemic stroke | 6 h | No |
Manual, 4 × 5′ Up to 20 mmHg above systolic BP |
Non-affected upper extremity |
Group1: one time. Group2: two times (repetition after 60 min). Group3: twice daily for 4 days. Control group: manual RIC simulation (30 mmHg) |
Trial feasibility at 90 days | Completed |
|
rtPA-RIC |
China | 2016 | 60 | 18–80 |
Clinical sign and symptoms of acute ischemic stroke and rtPA therapy candidate, NIHSS score ≥ 4 and ≤ 15 |
4.5 h | No |
Doctormate device, 5 × 5′ 200 mmHg |
Both upper extremities |
One time within 2 h after rtPA therapy Control group: not RIC simulation |
Infarct volume Infarct volume by MRI at 72 h | Recruiting |
|
REMOTE-CAT |
Spain | 2017 | 572 | > 18 |
Clinical signs and symptoms of acute ischemic stroke, RACE > 0, RACE motor > 0, known-onset stroke |
< 8 h | Yes |
Device, 5 × 5′, 200 mmHg |
Non-affected upper extremity |
One time in the ambulance Control group: RIC simulation (no pressure) |
Infarct volume by MRI at 72 h mRS at 90 days |
Recruiting |
|
TRIPCAIS |
China | 2017 | 120 | all | Confirmed ischemic stroke by neuroimaging, accordance with GTAIS and accomplish rtPA therapy | < 4.5 h | No |
RIPC Device, 5 × 5’ |
Non-affected upper extremity |
One time after rtPA therapy Control group: not RIC simulation |
VEGF and bFGF levels at 14 and 90 days | Recruiting |
|
REVISE-2 |
China | 2017 | 180 | 18–80 |
Confirmed Ischemic Stroke, NIHSS ≥6, Endovascular recanalization |
< 6 h | No |
Device, 4 × 5′ 200 mmHg |
Upper extremity |
One time Control group: RIC simulation (60 mmHg) |
Infarct volume at 3–7 days post-stroke | Not recruiting yet |
|
RICE PAC |
UK | 2017 | 60 | > 18 |
Ischemic Stroke, proximal anterior occlusion, endovascular recanalization |
< 6 h | No | Manual | Non-affected upper/lower extremity |
One time Control group: RIC simulation |
Infarct volume by MRI at 90 days | Not recruiting yet |
| REPOST [16] | Netherlands | 2017b | 200 | > 18 | Ischemic stroke | < 12 h | No |
Manual 4 × 5′ Up to 20 mmHg above systolic BP |
Upper extremity |
Twice daily × 4 days Control group: twice daily × 7 days (50 mmHg) |
Infarct volume by MRI at 4 days | Recruiting |
|
SERIC-AIS |
China | 2018 | 912 | 18–80 |
Confirmed Ischemic Stroke, NIHSS score > 5 and ≤ 25 |
< 12 h | No |
Device, 4 × 5′ 200 mmHg |
Both upper extremities |
Twice daily × 7 days Control group: twice daily × 7 days (60 mmHg) |
mRS at 90 days | Recruiting |
|
RICAMIS |
China | 2018 | 1800 | > 18 | Confirmed Ischemic Stroke by neuroimaging, NIHSS score ≥ 6 and ≤ 16 | 48 h | No | – | – |
Twice one day Control group: not RIC simulation |
Neurological score at 90 days | Recruiting |
|
RESIST [14] |
Denmark | 2018 | 1500 | > 18 | Clinical signs and symptoms of stroke, PreSS ≥1 | < 4 h | Yes |
Device, 5 × 5’, 200 mmHg |
Non-affected upper extremity |
Two times, one at the ambulance and one 6 h after in the hospital. Some patients get twice daily for 7 days. Control group: RIC simulation (20 mmHg) |
mRS at 90 days | Recruiting |
|
ICARUS |
US | 2018 | 10 | 18–85 |
Ischemic stroke, air transportation to a Stroke unit for endovascular recanalization, NIHSS ≥6 |
– | No |
Doctormate Device, 3–5 × 5′ 200 mmHg |
Both upper extremities |
One time in route (airplane) to Stroke center No control group |
Feasibility of delivering RLIC by air medical crews | Not recruiting yet |
|
SERICT-AIS |
China | 2019 | 50 | 18–80 |
Confirmed Ischemic Stroke and rtPA therapy, NIHSS score > 5 and ≤ 25 |
– | No |
Device, 4 × 5′ 200 mmHg |
Non-affected upper extremity |
Twice within 6–24 h from rtPA therapy, Control group: twice within 6–24 h from rtPA therapy (60 mmHg) |
Frequency of adverse events at 7 days or earlier | Not recruiting yet |
|
RIC-SIID |
China | 2019 | 30 | > 18 |
Confirmed Ischemic Stroke, NIHSS ≤15 |
< 48 h | No |
Device, 5 × 5′ 180 mmHg |
Upper extremity |
One time < 48 h from stroke symptom onset Control group: not RIC simulation |
Plasma levels of mHLA-DR at 2 and 7 days, pneumonia incidence within 7 days | Not recruiting yet |
|
PROTECT I |
France | 2019 | 126 | > 18 |
Ischemic Stroke, full occlusion of the MCA (occlusion of M1 and/or proximal M2), confirmed by MRA and DWI Endovascular recanalization |
< 6 h | No |
Device, 4 × 5′ 200 mmHg |
Upper extremity |
One time after first MRI Control group: RIC simulation (30 mmHg) |
Infarct volume by MRI after 24 h from endovascular recanalization | Not recruiting yet |
Abbreviations: bFGF Basic fibroblast growth factor, DWI Diffusion weighted imaging, GTAIS Guideline of thrombolysis in Acute Ischemic Stroke, MCA Middle cerebral artery, MRI Magnetic resonance imaging, mRS Modified Rankin Scale (mRS) Score, NIHSS National institute of Health Stroke Scale, PreSS Prehospital Stroke score, PWI-DWI Perfusion-weighted imaging-diffusion-weighted imaging, RACE Rapid arterial occlusion evaluation scale, RIC Remote ischaemic conditioning, RLIC Remote limb ischemic conditioning, rt-PA Recombinant tissue plasminogen activator, VEGF Vascular endothelial growth factor
aRegistered in ISRCTN
bRegistered in Netherlands Trial Register