NCT03481777

Remote Ischemic Conditioning in Patients With Acute Stroke (RESIST)

Remote Ischemic Conditioning in Patients With Acute Stroke: a Multicenter Randomized, Patient-assessor Blinded, Sham-controlled Study

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 1,500 (actual)
• Sponsor: Grethe Andersen · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Our primary aim is to investigate whether remote ischemic conditioning (RIC) as an adjunctive treatment can improve long-term recovery in acute stroke patients as an adjunct to standard treatment.

Detailed description

Stroke is the second-leading cause of death worldwide and a leading cause of serious, long-term disability. The most common type is acute ischemic stroke (AIS) which occurs in 85% of cases. Acute cerebral thromboembolism leads to an area of permanent damage (infarct core) in the most severely hypoperfused area and a surrounding area of impaired, yet salvageable tissue known as the "ischemic penumbra". Intravenous alteplase (IV tPA) and endovascular treatment (EVT) are approved acute reperfusion treatments of AIS to be started within the first 4½-6 hours (in some up to 24 hours) and as soon as possible after symptom onset to prevent the evolution of the infarct core. However, reperfusion itself may paradoxically result in tissue damage (reperfusion injury) and may contribute to infarct growth. Infarct progression can continue for days following a stroke, and failure of the collateral flow is a critical factor determining infarct growth. On the other hand, in intracerebral hemorrhage (ICH) the culprit is an eruption of blood into the brain parenchyma causing tissue destruction with a massive effect on adjacent brain tissues. Hematoma expansion as well as inflammatory pathways that are activated lead to further tissue damage, edema, and penumbral hypoperfusion. The prognosis after ICH is poor with a one-month mortality of 40%. Novel therapeutics and neuroprotective strategies that can be started ultra-early after symptom onset are urgently needed to reduce disability in both AIS and ICH. Ischemic conditioning is one of the most potent activators of endogenous protection against ischemia-reperfusion injury. Remote Ischemic Conditioning (RIC) can be applied as repeated short-lasting ischemia in a distant tissue that results in protection against subsequent long-lasting ischemic injury in the target organ. This protection can be applied prior to or during a prolonged ischemic event as remote ischemic pre-conditioning (RIPreC) and per-conditioning (RIPerC), respectively, or immediate after reperfusion as remote ischemic post-conditioning (RIPostC). RIC is commonly achieved by inflation of a blood pressure cuff to induce 5-minute cycles of limb ischemia alternating with 5 minutes of reperfusion. Preclinical studies show that RIC induces a promising infarct reduction in an experimental stroke model. Results from a recent proof-of-concept study at our institution indicate that RIPerC applied during ambulance transportation as an adjunctive to in-hospital IV tPA increases brain tissue survival after one month. Furthermore, RIPerC patients had less severe neurological symptoms at admission and tended to have decreased perfusion deficits. To-date, no serious adverse events have been documented in RIC. RIC is a non-pharmacologic and non-invasive treatment without noticeable discomfort that has first-aid potential worldwide. However, whether combined remote ischemic per- and postconditioning can improve long-term recovery in AIS and ICH has never been investigated in a randomized controlled trial.

Conditions

• Stroke, Acute
• Ischemic Stroke
• Hemorrhagic Stroke
• Intracerebral Hemorrhage
• Cerebrovascular Disorders
• Central Nervous System Diseases

Interventions

Type	Name	Description
DEVICE	Remote Ischemic Conditioning	RIC is commonly achieved by inflation of a blood pressure cuff to induce 5-minute cycles of limb ischemia alternating with 5 minutes of reperfusion.
DEVICE	Sham Remote Ischemic Conditioning	Sham Comparator (Sham-RIC)

Timeline

• Start date: 2018-03-15
• Primary completion: 2023-02-03
• Completion: 2023-02-03
• First posted: 2018-03-29
• Last updated: 2025-01-27
• Results posted: 2025-01-27

Locations

4 sites across 1 country: Denmark