Efficacy Study II on Remote Ischemic Preconditioning for the Prevention of Stroke-Associated Pneumonia (RICA-2)

Multicenter, Randomized, Double-blind, Placebo-controlled Clinical Study on the Efficacy and Safety of Remote Ischemic Conditioning in Preventing Stroke-related Pneumonia

Verifying whether remote ischemic adaptation can reduce the occurrence of stroke related pneumonia in acute stroke patients within 24 hours of onset

Study Overview

• Status: Recruiting
• Conditions: Stroke
• Intervention / Treatment: Device: Remote ischemic conditioning; Device: Sham remote ischemic conditioning

Detailed Description

Verifying whether remote ischemic adaptation can reduce the occurrence and safety of stroke related pneumonia in acute stroke patients within 24 hours of onset

• Study Type: Interventional
• Enrollment (Estimated): 1650
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xunming Ji, M.D. Ph.D; Phone Number: 861013120136877; Email: jixunming@vip.163.com; 1730812302@qq.com
• Study Contact Backup: Name: Lina Jia, M.D.; Phone Number: +8615901588600; Email: 1730812302@qq.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Xuanwu Hospital, Capital Medical University
    • Contact: Xunming Ji, M.D., Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age≥18 years old;
• Diagnosis of acute ischemic stroke;
• Remote ischemic conditioning or sham-remote ischemic conditioning can be treated within 24 hours after stroke onset
• NIHSS score≥4;
• Subject or his or her legally authorized representative was able to provide informed consent.

Exclusion Criteria:

• During the screening period, body temperature ≥ 38 ℃;
• Evidence of lung infection, urinary tract infection or other infectious diseases during the screening period
• Expected lifespan less than 7 days
• Mechanical ventilation is expected to be required within 7 days;
• Anti-infective drug were used within 7 days prior to stroke;
• Uncontrolled hypertension with medication (defined as systolic blood pressure ≥200 mmHg and/or diastolic blood pressure ≥110 mmHg);
• There are contraindications for remote ischemic conditioning (such as skin and soft tissue injury, fractures, peripheral arterial disease, etc. in the upper limbs);
• History of autoimmune disease or malignancies;
• Use of immunosuppressive drug within the preceding 3 months;
• Pregnant or lactating, or pregnancy test positive;
• Current participation in another investigational trial;
• Other conditions are not suitable for this trial as evaluated by researchers.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention group; Remote ischemic conditioning (RIC) -200mmHg and best medical management	Device: Remote ischemic conditioning; The RIC procedure consists of five cycles of unilateral arm ischemia for 5 minutes, which was followed by reperfusion for another 5 minutes. The procedure is performed with an electric, autocontrol device with a cuff that inflated to a pressure of 200 mmHg during the ischemia period. RIC is performed within 24hours after stroke onset, and twice daily for the subsequent 7 days.
Sham Comparator: Sham group; Remote ischemic conditioning (RIC) -60mmHg and best medical management	Device: Sham remote ischemic conditioning; The RIC procedure consists of five cycles of unilateral arm ischemia for 5 minutes, which was followed by reperfusion for another 5 minutes. The procedure is performed with an electric, autocontrol device with a cuff that inflated to a pressure of 60 mmHg during the ischemia period. RIC is performed within 24hours after stroke onset, and twice daily for the subsequent 7 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stroke-associated pneumonia	Stroke-associated pneumonia incidence rate	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physician diagnosed pneumonia	Physician diagnosed pneumonia incidence rate	7 days
Physician diagnosed pneumonia	Physician diagnosed pneumonia incidence rate	8-90 days
Urinary tract infections	Urinary tract infections incidence rate	7 days
Infections	Infections incidence rate	7 days
All-cause mortality	All-cause mortality incidence rate	90 days
Inpatient days	Total inpatient days	90 days
Modified Rankin scale score from 0 to 1	In medical and clinical research, the modified Rankin Scale (mRS) is used to assess the degree of disability in patients after a stroke. The scale ranges from 0 to 6, where 0 indicates no symptoms and 6 indicates death. On the mRS scale, scores from 0 to 2 usually indicate no or slight disability. Specifically: 0 points: No symptoms.; point: Symptoms present but no significant disability; able to carry out all usual duties and activities.; points: Slight disability; able to look after own affairs without assistance but unable to carry out all previous activities. Therefore, in clinical research, if a treatment or intervention increases the proportion of patients scoring 0 to 1 on the mRS scale, it is generally considered a positive outcome. This means that more patients have a better functional status and lower degree of disability after treatment.	90 days after the onset of symptoms
Modified Rankin scale score from 0 to 2	In medical and clinical research, the modified Rankin Scale (mRS) is used to assess the degree of disability in patients after a stroke. The scale ranges from 0 to 6, where 0 indicates no symptoms and 6 indicates death. On the mRS scale, scores from 0 to 2 usually indicate no or slight disability. Specifically: 0 points: No symptoms.; point: Symptoms present but no significant disability; able to carry out all usual duties and activities.; points: Slight disability; able to look after own affairs without assistance but unable to carry out all previous activities. Therefore, in clinical research, if a treatment or intervention increases the proportion of patients scoring 0 to 2 on the mRS scale, it is generally considered a positive outcome. This means that more patients have a better functional status and lower degree of disability after treatment.	90 days
Modified Rankin scale scores	Shift analysis. In medical and clinical research, the modified Rankin Scale (mRS) is used to assess the degree of disability in patients after a stroke. The scale ranges from 0 to 6, where 0 indicates no symptoms and 6 indicates death. On the mRS scale, scores from 0 to 2 usually indicate no or slight disability. Specifically: 0 points: No symptoms.; point: Symptoms present but no significant disability; able to carry out all usual duties and activities.; points: Slight disability; able to look after own affairs without assistance but unable to carry out all previous activities. Therefore, in clinical research, if a treatment or intervention increases the proportion of patients scoring 0 to 2 on the mRS scale, it is generally considered a positive outcome. This means that more patients have a better functional status and lower degree of disability after treatment.	90 days
EQ-5D-5L scores	The scores of EQ-5D-5L. The five dimensions included in EQ-5D-5L are: Mobility: This dimension assesses the person's ability to walk about. Self-Care: This evaluates the individual's ability to wash or dress themselves. Usual Activities: This covers work, study, housework, family or leisure activities. Pain/Discomfort: This measures the level of pain or discomfort experienced by the individual. Anxiety/Depression: This assesses the person's psychological state, in terms of levels of anxiety or depression. Each of these five dimensions has five levels of severity: Level 1: No problems Level 2: Slight problems Level 3: Moderate problems Level 4: Severe problems Level 5: Extreme problems	90 days
NIHSS stroke scale scores	The scores of NIHSS stroke scale. The total NIHSS score can range from 0 to 42, with: 0: Indicating no stroke symptoms. 1-4: Indicating a minor stroke. 5-15: Indicating a moderate stroke. 16-20: Indicating a moderate to severe stroke. 21-42: Indicating a severe stroke. The NIHSS is useful in evaluating the effect of acute stroke treatments, predicting patient outcomes, and assessing the progression of stroke symptoms.	24 hours
NIHSS stroke scale scores	The scores of NIHSS stroke scale. The total NIHSS score can range from 0 to 42, with: 0: Indicating no stroke symptoms. 1-4: Indicating a minor stroke. 5-15: Indicating a moderate stroke. 16-20: Indicating a moderate to severe stroke. 21-42: Indicating a severe stroke. The NIHSS is useful in evaluating the effect of acute stroke treatments, predicting patient outcomes, and assessing the progression of stroke symptoms.	7 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Spots of skin bleeding within 7 days	Number of subjects who have skin bleeding points within 7 days	7 days
Red or swollen arms within 7 days	Number of subjects who have red or swollen arms within 7 days	7 days
Dizziness within 7 days	Number of subjects who have dizziness within 7 days	7 days
Nausea within 7 days	Number of subjects who have nausea within 7 days	7 days
Palpitations within 7 days.	Number of subjects who have palpitations within 7 days.	7 days

Collaborators and Investigators

• Sponsor: Capital Medical University
• Investigators: Study Director: Chuanjie Wu, M.D., Xuanwu Hospital of Capital Medical University

Publications and helpful links

General Publications

• Iadecola C, Anrather J. The immunology of stroke: from mechanisms to translation. Nat Med. 2011 Jul 7;17(7):796-808. doi: 10.1038/nm.2399.
• Westendorp WF, Vermeij JD, Zock E, Hooijenga IJ, Kruyt ND, Bosboom HJ, Kwa VI, Weisfelt M, Remmers MJ, ten Houten R, Schreuder AH, Vermeer SE, van Dijk EJ, Dippel DW, Dijkgraaf MG, Spanjaard L, Vermeulen M, van der Poll T, Prins JM, Vermeij FH, Roos YB, Kleyweg RP, Kerkhoff H, Brouwer MC, Zwinderman AH, van de Beek D, Nederkoorn PJ; PASS investigators. The Preventive Antibiotics in Stroke Study (PASS): a pragmatic randomised open-label masked endpoint clinical trial. Lancet. 2015 Apr 18;385(9977):1519-26. doi: 10.1016/S0140-6736(14)62456-9. Epub 2015 Jan 20.
• Kalra L, Irshad S, Hodsoll J, Simpson M, Gulliford M, Smithard D, Patel A, Rebollo-Mesa I; STROKE-INF Investigators. Prophylactic antibiotics after acute stroke for reducing pneumonia in patients with dysphagia (STROKE-INF): a prospective, cluster-randomised, open-label, masked endpoint, controlled clinical trial. Lancet. 2015 Nov 7;386(10006):1835-44. doi: 10.1016/S0140-6736(15)00126-9. Epub 2015 Sep 3.
• Hoffmann S, Harms H, Ulm L, Nabavi DG, Mackert BM, Schmehl I, Jungehulsing GJ, Montaner J, Bustamante A, Hermans M, Hamilton F, Gohler J, Malzahn U, Malsch C, Heuschmann PU, Meisel C, Meisel A; PREDICT Investigators. Stroke-induced immunodepression and dysphagia independently predict stroke-associated pneumonia - The PREDICT study. J Cereb Blood Flow Metab. 2017 Dec;37(12):3671-3682. doi: 10.1177/0271678X16671964. Epub 2016 Oct 14.
• Chamorro A, Meisel A, Planas AM, Urra X, van de Beek D, Veltkamp R. The immunology of acute stroke. Nat Rev Neurol. 2012 Jun 5;8(7):401-10. doi: 10.1038/nrneurol.2012.98.
• Chamorro A, Urra X, Planas AM. Infection after acute ischemic stroke: a manifestation of brain-induced immunodepression. Stroke. 2007 Mar;38(3):1097-103. doi: 10.1161/01.STR.0000258346.68966.9d. Epub 2007 Jan 25.
• Randhawa PK, Bali A, Jaggi AS. RIPC for multiorgan salvage in clinical settings: evolution of concept, evidences and mechanisms. Eur J Pharmacol. 2015 Jan 5;746:317-32. doi: 10.1016/j.ejphar.2014.08.016. Epub 2014 Aug 28.

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2024
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: August 1, 2023
• First Submitted That Met QC Criteria: August 1, 2023
• First Posted (Actual): August 8, 2023

Study Record Updates

• Last Update Posted (Estimated): January 23, 2024
• Last Update Submitted That Met QC Criteria: January 22, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Stroke; Pneumonia
• Other Study ID Numbers: RICA-2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No