Clinical trial NCT04345445: Study to Evaluate the Efficacy and Safety of Tocilizumab Versus Corticosteroids in Hospitalised COVID-19 Patients With High Risk of Progression
Official title: An Open-label, Randomized, Cross-over Interventional Study to Evaluate the Efficacy and Safety of Tocilizumab Versus Corticosteroids in Hospitalised COVID-19 Patients With High Risk of Progression
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: COVID-19
Keywords: COVID-19
Lead sponsor: University of Malaya
Sponsor class: OTHER
First posted: 2020-04-14
Enrollment: 310
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This study aims to compare the efficacy and safety of Methylprednisolone versus Tocilizumab in improving clinical outcomes and reducing the need for ventilator support in COVID-19 patients with moderate COVID-19 disease at risk for complications of cytokine storm. Approximately 310 participants hospitalized with COVID-19 in UMMC, Hospital Sungai Buloh, Hospital Kuala Lumpur and Hospital Tuanku Jaafar will be enrolled into this study.

Eligible participants will be selected based on a set of clinical, laboratory and radiological parameters indicative of early stages of CRS and lung function decline prior to being randomized at a ratio of 1:1 to receive either Tocilizumab or Methylprednisolone. Participants will be monitored daily for clinical and laboratory parameters, and at 48 hours, switched to the alternate study arm should they manifest signs and symptoms indicative of decompensation.


Eligibility criteria: Inclusion Criteria:

1) Hospitalised symptomatic COVID-19 patients 2( Presence of clinical and radiological signs of progressive disease, AND laboratory evidence indicative of risk for cytokine storm complications.

All patients participating in this clinical trial must meet the following inclusion criteria:

1. Hospitalised symptomatic COVID-19 patients
2. Presence of clinical and radiological signs of progressive disease, AND laboratory evidence indicative of risk for cytokine storm complications:

   Clinical:

   Dyspnoea OR RR\>20 breaths/min AND O2 sat \<93% on RA OR increasing need for O2 supplementation to maintain O2 sat \>95% on RA

   WITH

   Radiological:

   CXR or CT indicative of pneumonia OR worsening findings over time

   AND

   Laboratory:

   CRP levels \>60 OR an increase of CRP \>20 over 12 hours WITH an increasing ferritin level OR declining lymphocyte counts
3. Age \> 18 years and able to give consent

Exclusion Criteria:

Patients will be excluded if any of the following conditions apply:

1. Known sensitivity/allergy to TCZ or other monoclonal antibodies
2. AST/ALT\>5 times UNL, platelet counts \<50,000 or neutrophil counts \<500
3. Active TB
4. Pregnant
5. Receipt of mechanical ventilation
6. Has received other immunomodulatory drugs (including TCZ) in the past for the treatment of other conditions
7. Individuals, in the opinion of the investigator, where progression to death is imminent and inevitable in the next 24 hours irrespective of treatment provision or who have signed a DNR.
8. Participating in other clinical trials (subject to approval)
9. Any serious medical condition or abnormal clinical laboratory tests which in the judgement of the investigator may compromise patient safety should he/she participate in the study.

Primary outcomes:
measure: The proportion of patients requiring mechanical ventilation
timeFrame: Through study completion, and average of 6 months
measure: Mean days of ventilation
timeFrame: Through study completion, and average of 6 months
Secondary outcomes:
measure: The proportion of patients requiring ICU admission
timeFrame: Through study completion, and average of 6 months
measure: Overall 28-day survival
timeFrame: 28 day from baseline
measure: Change in symptom severity assessed by the World Health Organization (WHO) Coronavirus Disease 2019 (COVID19) ordinal scale measured daily up to 7 days from baseline
timeFrame: 7 days from baseline
measure: Duration of hospital and ICU stay
timeFrame: Through study completion, and average of 6 months
Other outcomes:
Locations:
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
Study officials:
References: