Dataset Information

Effect of Remote Ischaemic Conditioning on the Inflammatory Cytokine Cascade of COVID-19 (RIC in COVID-19): a Randomized Controlled Trial.

ABSTRACT:

Purpose

Patients hospitalized with COVID-19 may develop a hyperinflammatory, dysregulated cytokine "storm" that rapidly progresses to acute respiratory distress syndrome, multiple organ dysfunction, and even death. Remote ischaemic conditioning (RIC) has elicited anti-inflammatory and cytoprotective benefits by reducing cytokines following sepsis in animal studies. Therefore, we investigated whether RIC would mitigate the inflammatory cytokine cascade induced by COVID-19.

Methods

We conducted a prospective, multicentre, randomized, sham-controlled, single-blind trial in Brazil and South Africa. Non-critically ill adult patients with COVID-19 pneumonia were randomly allocated (1:1) to receive either RIC (intermittent ischaemia/reperfusion applied through four 5-min cycles of inflation (20 mmHg above systolic blood pressure) and deflation of an automated blood-pressure cuff) or sham for approximately 15 days. Serum was collected following RIC/sham administration and analyzed for inflammatory cytokines using flow cytometry. The endpoint was the change in serum cytokine concentrations. Participants were followed for 30 days.

Results

Eighty randomized participants (40 RIC and 40 sham) completed the trial. Baseline characteristics according to trial intervention were overall balanced. Despite downward trajectories of all cytokines across hospitalization, we observed no substantial changes in cytokine concentrations after successive days of RIC. Time to clinical improvement was similar in both groups (HR 1.66; 95% CI, 0.938-2.948, p 0.08). Overall RIC did not demonstrate a significant impact on the composite outcome of all-cause death or clinical deterioration (HR 1.19; 95% CI, 0.616-2.295, p = 0.61).

Conclusion

RIC did not reduce the hypercytokinaemia induced by COVID-19 or prevent clinical deterioration to critical care.

Trial registration

ClinicalTrials.gov Identifier: NCT04699227.

SUBMITTER: Lukhna K

PROVIDER: S-EPMC9707178 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effect of Remote Ischaemic Conditioning on the Inflammatory Cytokine Cascade of COVID-19 (RIC in COVID-19): a Randomized Controlled Trial.

Lukhna Kishal K do Carmo Helison R P HRP Castillo Alejandro Rossell AR Davidson Sean M SM Geffen Hayli H Giesz Sara S Golforoush Pelin P Bovi Ticiane Gonçalez TG Gorag Diana D Salama Alan A Imamdin Aqeela A Kalkhoran Siavash S Lecour Sandrine S Perroud Mauricio W MW Ntsekhe Mpiko M Sposito Andrei C AC Yellon Derek M DM

Cardiovascular drugs and therapy 20221129 3

<h4>Purpose</h4>Patients hospitalized with COVID-19 may develop a hyperinflammatory, dysregulated cytokine "storm" that rapidly progresses to acute respiratory distress syndrome, multiple organ dysfunction, and even death. Remote ischaemic conditioning (RIC) has elicited anti-inflammatory and cytoprotective benefits by reducing cytokines following sepsis in animal studies. Therefore, we investigated whether RIC would mitigate the inflammatory cytokine cascade induced by COVID-19.<h4>Methods</h4> ...[more]

PMID: 36445625

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Project description:IntroductionRemote ischaemic conditioning (RIC) refers to the use of controlled transient ischemic and reperfusion cycles, commonly of the upper or lower limb, to mitigate cellular damage from ischaemic injury. Preclinical studies demonstrate that RIC may have a neuroprotective effect and therefore could represent a novel therapeutic option in the management of neurological disorders. The aim of this review is to comprehensively describe the current clinical evidence of RIC in neurological disorders.MethodsA computerised search of EMBASE and OVID MEDLINE was conducted from 2002 to October 2023 for randomised controlled trials (RCTs) investigating RIC in neurological diseases.ResultsA total of 46 different RCTs in 12 different neurological disorders (n = 7544) were included in the analysis. Conditions included acute ischaemic stroke, symptomatic intracranial stenosis and vascular cognitive impairment. The most commonly used RIC protocol parameters in the selected studies were as follows: cuff pressure at 200 mmHg (27 trials), 5-min cycle length (42 trials), 5 cycles of ischaemia and reperfusion (24 trials) and the application to the upper limb unilaterally (23 trials).ConclusionsThe comprehensive analysis of the included studies reveals promising results regarding the safety and therapeutic effect of RIC as an option for managing neurological diseases. Particularly, the strongest evidence supports its potential use in chronic stroke patients and vascular cognitive impairment. The neuroprotective effects of RIC, as demonstrated in preclinical studies, suggest that this therapeutic approach could extend its benefits to various other diseases affecting the nervous system. However, to establish the efficacy of RIC across different neurological disorders, further trials with larger sample sizes and more diverse patient populations are warranted. Upcoming trials are expected to provide valuable evidence that will not only confirm the efficacy of RIC in neurological disease management but also help identify the most optimal RIC regimen for specific conditions.

Dataset Information

Effect of Remote Ischaemic Conditioning on the Inflammatory Cytokine Cascade of COVID-19 (RIC in COVID-19): a Randomized Controlled Trial.

Purpose

Methods

Results

Conclusion

Trial registration

Publications

Effect of Remote Ischaemic Conditioning on the Inflammatory Cytokine Cascade of COVID-19 (RIC in COVID-19): a Randomized Controlled Trial.

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