RIC as an Adjunct Therapy for Severe COVID-19 Disease: a Prospective Randomized Pilot Study

NCT04659460 | Unknown

• 1 other identifier: 1.4
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

This research aims to assess the use of an experimental and non-invasive procedure, Remote Ischemic Conditioning (RIC), as an adjunct therapy in attenuating severe COVID-19 disease. An excessive and counterproductive systemic inflammatory response is thought to be a major cause of severe disease and death in patients with COVID-19. Severe ICU cases frequently have markedly higher levels of inflammatory markers such as CRP, IL-6, IL and TNF-a; which is thought to be correlated with increasing disease severity. The relationship between dysregulated inflammatory processes and disease states such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are well understood. ALI is characterized by an acute exaggerated mononuclear/neutrophilic inflammatory response followed by progressive collagen deposition in the lung, and if severe enough, may progress to ARDS requiring ventilation.

Conditions

COVID; Corona Virus Infection; Acute Lung Injury; Ischemia Limb; Acute Respiratory Distress Syndrome

Keywords

Remote Ischemic Conditioning; Inflammatory response

Outcome Measures

Primary Outcomes (9)

• Interleukin 1-Beta (IL-1B) (pg/mL)

  Serum concentration, to be collected immediately before RIC treatment, treatment plus 6 hours, treatment plus 12 hours, treatment plus 24 hours, and treatment plus 48 hours (+/- 1 hour at each 0+ time point)

  Through study completion - up to 12 months

• Interleukin 6 (IL-6) (pg/mL)

  Serum concentration, to be collected immediately before RIC treatment, treatment plus 6 hours, treatment plus 12 hours, treatment plus 24 hours, and treatment plus 48 hours (+/- 1 hour at each 0+ time point)

  Through study completion - up to 12 months

• C-reactive protein (CRP) (mg/mL)

  Serum concentration, to be collected immediately before RIC treatment, treatment plus 6 hours, treatment plus 12 hours, treatment plus 24 hours, and treatment plus 48 hours (+/- 1 hour at each 0+ time point)

  Through study completion - up to 12 months

• Tumour Necrosis Factor Alpha (TNFa) (pg/mL)

  Serum concentration, to be collected immediately before RIC treatment, treatment plus 6 hours, treatment plus 12 hours, treatment plus 24 hours, and treatment plus 48 hours (+/- 1 hour at each 0+ time point)

  Through study completion - up to 12 months

• Neutrophil to Lymphocyte Ratio (NLR) (absolute neutrophils/lymphocytes)

  Serum concentration, to be collected immediately before RIC treatment, treatment plus 6 hours, treatment plus 12 hours, treatment plus 24 hours, and treatment plus 48 hours (+/- 1 hour at each 0+ time point)

  Through study completion - up to 12 months

• Serum Ferritin (ng/mL)

  Serum concentration, to be collected immediately before RIC treatment, treatment plus 6 hours, treatment plus 12 hours, treatment plus 24 hours, and treatment plus 48 hours (+/- 1 hour at each 0+ time point)

  Through study completion - up to 12 months

• International Normalized Ratio (INR)

  Standard coagulation parameter, to be collected immediately before RIC treatment, treatment plus 6 hours, treatment plus 12 hours, treatment plus 24 hours, and treatment plus 48 hours (+/- 1 hour at each 0+ time point)

  Through study completion - up to 12 months

• Prothrombin Time (PTT)

  Standard coagulation parameter, to be collected immediately before RIC treatment, treatment plus 6 hours, treatment plus 12 hours, treatment plus 24 hours, and treatment plus 48 hours (+/- 1 hour at each 0+ time point)

  Through study completion - up to 12 months

• Rotational Thromboelastometry (ROTEM)

  ROTEM coagulation assessment using the commercial ROTEM device traditionally used for the assessment of coagulopathy, to be collected immediately before RIC treatment, treatment plus 6 hours, treatment plus 12 hours, treatment plus 24 hours, and treatment plus 48 hours (+/- 1 hour at each 0+ time point).

  Through study completion - up to 12 months

Secondary Outcomes (3)

• Total duration of mechanical ventilation (number of days)

  Through study completion - up to 12 months

• Intensive Care Unit Length of Stay (number of days)

  Through study completion - up to 12 months

• Hospital Length of Stay (number of days)

  Through study completion - up to 12 months

Study Arms (2)

Remote Ischemic Conditioning

EXPERIMENTAL

RIC interventions will be applied to the upper extremity for a total of 20 cumulative minutes of limb ischemia, at a pressure of 250 mmHg.

Device: Remote Ischemic Conditioning

Sham Remote Ischemic Conditioning

SHAM COMPARATOR

RIC sham interventions will be applied to the upper extremity for a total of 20 cumulative minutes. For sham, inflation will occur.

Device: Remote Ischemic Conditioning

Interventions

Remote Ischemic Conditioning DEVICE

RIC interventions will be applied to the upper extremity calibrated to induce four, ten-minute cycles of five-minutes-ischemia and five-minutes-perfusion for a total of 20 cumulative minutes of limb ischemia, at a pressure of 250 mmHg.

Remote Ischemic Conditioning; Sham Remote Ischemic Conditioning

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 16 years old
• Admission to ICU
• Either confirmed positive, or presumed, COVID-19 disease
• Radiological evidence of COVID-related pneumonia (CXR or CT abnormalities indicating COVID-19 pneumonia; such as, ground-glass opacities)
• Able to safely undergo conditioning of the arm
• No peripheral vascular disease
• No evidence of prior arm surgery
• No evidence of prior radiation or lymph node dissection
• Clinical staff deems it safe to proceed (Yes/No: signed by MRP)

You may not qualify if:

• Age \<16 years
• Unable to safely undergo conditioning
• Known peripheral vascular disease
• Evidence of prior arm surgery
• Evidence of prior radiation or lymph node dissection
• Clinical staff deems it unsafe (Yes/No: signed by MRP)
• No radiological evidence of COVID-related pneumonia
• Anti-coagulation drug use

Sponsors & Collaborators

• Unity Health Toronto: lead
• Defence Research and Development Canada: collaborator

MeSH Terms

Conditions

Coronavirus Infections; Acute Lung Injury; Respiratory Distress Syndrome

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Lung Injury; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Central Study Contacts

Sandy Trpcic

CONTACT

4168646060; Sandy.Trpcic@unityhealth.to

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Only Research Assistant will be unblinded. Participant, clinical team, PI, etc. will all be blinded to the randomization group.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single-centre, randomized controlled pilot study

Study Record Dates

• First Submitted: July 3, 2020
• First Posted: December 9, 2020
• Study Start: December 15, 2020
• Primary Completion: March 31, 2021
• Study Completion: September 1, 2021
• Last Updated: December 9, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share