COVID-19: Salvage TOcilizumab as a Rescue Measure (COVIDSTORM)

COVID-19: Salvage TOcilizumab as a Rescue Measure. Use of Tocilizumab in the Inflammatory Phase of COVID-19 / New Coronavirus Disease

Evaluating the efficacy of Tocilizumab in hospitalized patients in the inflammatory phase of COVID-19. Randomization 2:1 (TCZ:standard of care).

Study Overview

• Status: Completed
• Conditions: Covid19
• Intervention / Treatment: Drug: iv Tocillizumab (TCZ)

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 3

Contacts and Locations

Study Locations

• Finland
  • Turku, Finland, 20521
    • Turku University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• written informed consaent obtained
• hospitalized with COVID-19 disease
• Age >/= 18 years
• SARS CoV-2 NhO posit
• Sp=2 </93% on ambient air or respiratory rate >30 /min
• Any 2 of the 4: P-IL-6 > 2 x ULN / P-ferritin > 2 x ULN / P-FIDD >1.5 mg/l / P- CRP >40 mg/l without obvious presence of bacterial infection (normal values: P -IL-6 <5.9 ng/l; P-ferritin, men 30-400 mikrog/l, women 13-150 mikrog/l ; P-FIDD (Fibrin degradation products, D-dimer) <0.5 mg/l; P-CRP <10 mg/l)

Exclusion Criteria:

• Known severe allergic reactions to monoclonal antibodies
• Active confirmed tuberculosis with ongoing treatment or obvious tuberculosis or obvious other bacterial, fungal or viral infection (besides COVID-19)
• In the opinion of the clinical team, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments
• Long-term oral anti-rejection or immunomodulatory drugs (including corticosteroids equivalent to methylprednison 15mg/day)
• Pregnant or lactating women. If needed, exclusion of pregnancy should be performed by laboratory test (U-hCG-O).
• Participating in other drug clinical trials
• Absolute neutrophil count < 1 x10E9/l
• Platelet count <50 x10E9/l
• ALAT >10x ULN

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tocilizumab (TCZ); Participants will receive one infusion of iv TCZ (according to weight of patient)	Drug: iv Tocillizumab (TCZ); Participants are randomized (2:1) to receive TCZ or Standard of Care
No Intervention: standard of care (no TCZ); Participants will receive standard of care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical status at day 28	(assessed using 7-category ordinal scale) 7 death 6 in ICU with ECMO/ mechanical ventilation 5 in ICU, no ECMO/ mechanical ventilation 4 in hospital, not ICU, needs supplementary oxygen 3 in hospital, not ICU, no supplementary oxygen 2 not in hospital, but not back to normal 1 not in hospital, back to normal	day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to clinical improvement	defined as a National Early Warning Score 2 (NEWS2) of>/=2 maintained for 24 hours	28 days
Time to decline of at least 2 categories	relative on a 7-category ordinalscale of clinical status	28 days
Incidence of mechanical and/or non-invasive ventilation	(mode and duration of respiratory support) Hospital day when respiratory support needed with non-invasive ventilation - and duration. Hospital day when respiratory support needed by invasive mechanical ventilation -and duration.	28 days
Number of ventilator-free days to day 28	days not in ventilator	28 days
Organ failure free days to day 28	days without organ failure	28 days
Incidence of ICU stay	ICU admission day	28 days
Duration of ICU stay	days on ICU	28 days
Time to clinical failure	time to death, mechanical ventilation, or ICU admission (whichever occurs first)	28 days
SAPS II	during ICU stay SAPS II = simplified acute physiology score II min 0 (best), max 163 (worst)	28 days
CCI	during ICU stay CCI = Charlson Comorbidity Index min 0 (best), max 37 (worst)	28 days
APACHE II	during ICU stay APACHE II = acute physiology and chronic health evaluation II min 0 (best), max 71 (worst)	28 days
SOFA 6	during ICU stay SOFA 6 = sequential organ failure assessment min 0 (best), max 24 (worst)	28 days
Mortality rate	during and end of period of 28 days	28 days
Time to hospital discharge or "ready for discharge"	as evidenced by normal body temperature and respiratory rate and stable oxygen saturation on ambient air or </=2 l supplemental oxygen	28 days
Duration of supplemental oxygen	days on suppl oxygen	28 days

Collaborators and Investigators

• Sponsor: Jarmo Oksi

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2020
• Primary Completion (Actual): June 16, 2021
• Study Completion (Actual): June 16, 2021

Study Registration Dates

• First Submitted: September 3, 2020
• First Submitted That Met QC Criteria: October 5, 2020
• First Posted (Actual): October 8, 2020

Study Record Updates

• Last Update Posted (Actual): June 21, 2021
• Last Update Submitted That Met QC Criteria: June 17, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: COVID-19; tocilizumab; new coronavirus disease
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: EudraCT 2020-002039-31; 2020-002039-31 (EudraCT Number); T124/2020 (Other Identifier: Turku University Hospital); KLnro 36/2020 (Other Identifier: Fimea); dnro 68/06.00.01/2020 (Other Identifier: TUKIJA / VALVIRA)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: plan to investigate if it is possible by law

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No