RIC in COVID-19—a Clinical Trial to Investigate Whether Remote Ischemic Conditioning (RIC) Can Prevent Deterioration to Critical Care in Patients with COVID-19

Abstract

Purpose Coronavirus disease 19 (COVID-19) has, to date, been diagnosed in over 130 million persons worldwide and is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several variants of concern have emerged including those in the United Kingdom, South Africa, and Brazil. SARS-CoV-2 can cause a dysregulated inflammatory response known as a cytokine storm, which can progress rapidly to acute respiratory distress syndrome (ARDS), multi-organ failure, and death. Suppressing these cytokine elevations may be key to improving outcomes. Remote ischemic conditioning (RIC) is a simple, non-invasive procedure whereby a blood pressure cuff is inflated and deflated on the upper arm for several cycles. “RIC in COVID-19” is a pilot, multi-center, randomized clinical trial, designed to ascertain whether RIC suppresses inflammatory cytokine production. Methods A minimum of 55 adult patients with diagnosed COVID-19, but not of critical status, will be enrolled from centers in the United Kingdom, Brazil, and South Africa. RIC will be administered daily for up to 15 days. The primary outcome is the level of inflammatory cytokines that are involved in the cytokine storm that can occur following SARS-CoV-2 infection. The secondary endpoint is the time between admission and until intensive care admission or death. The in vitro cytotoxicity of patient blood will also be assessed using primary human cardiac endothelial cells. Conclusions The results of this pilot study will provide initial evidence on the ability of RIC to suppress the production of inflammatory cytokines in the setting of COVID-19. Trial Registration NCT04699227, registered January 7th, 2021.

Phenotypic changes in low-density lipoprotein particles as markers of adverse clinical outcomes in COVID-19

“…Patients enrolled in this study were the Brazilian subgroup of patients who participated in the RIC in COVID-19 trial [ 16 ], for whom a remote ischemia and reperfusion stimulus on the brachial artery was neutral on both inflammatory and clinical outcomes [ 17 ]. The study protocol was registered on the public trials database clinicaltrials.gov NCT04699227 .…”

“…All details regarding the inclusion and exclusion criteria and tests performed were previously described [ 16 ]. Briefly, inclusion criteria included: (i) adult patients (≥18 to 80 years of age) with a diagnosis of COVID-19 infection; (ii) clinical features of respiratory distress (respiratory rate > 30 bpm or use of accessory muscles); (iii) peripheral oxygen saturation SaO 2 < 95% or requiring oxygen supplementation; (iv) clinically unwell with reduced mobility, raised temperature/heart rate, and/or deranged biochemical laboratory results.…”

Remote ischaemic conditioning: defining critical criteria for success—report from the 11th Hatter Cardiovascular Workshop

“…Sepsis is associated with an increase in cytokines similar to that observed in patients diagnosed with COVID-19 [ 74 ]. This particular question is being investigated in a clinical study designed to ascertain whether RIC can reduce cytokine levels and prevent deterioration to critical care in patients with COVID-19, and we await the outcome of the clinical studies [ 21 ].…”

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

“…All participants provided written informed consent before randomization. Details of the trial rationale and design have been previously published [29], and a copy of the protocol is available.…”