A Multi-center, Randomized Controlled, Phase III Study to evaluate the Clinical Outcomes and Safety of Tocilizumab along with
Standard of Care in Patients with Cytokine Release Syndrome associated with COVID-19 infection
Trial Acronym
COVINTOC
Secondary IDs if Any
Secondary ID
Identifier
TCZ/COVID-19/01/2020 Version 2.0 dated 05 May 2020
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Arvinder Soin
Designation
National lead Investigator
Affiliation
Medanta Institute of Education and Research (MIER)
Address
Medanta-The Medicity Sector – 38, Gurgaon, Haryana-122001, India
Gurgaon HARYANA 122001 India
Phone
01244855100
Fax
01244834111
Email
avisoin1@gmail.com
Details of Contact Person Scientific Query
Name
Dr Pooja Sharma
Designation
Senior Scientist and Head MIER
Affiliation
Medanta Institute of Education and Research (MIER)
Address
Medanta-The Medicity Sector-38, Gurgaon, Haryana-122001, India
Gurgaon HARYANA 122001 India
Phone
01244855100
Fax
01244834111
Email
pooja.sharma@medanta.org
Details of Contact Person Public Query
Name
Kuldeep K Chauhan
Designation
Senior Clinical Project Leader- Research Operations
Affiliation
Medanta Institute of Education and Research (MIER)
Address
Medanta-The Medicity Sector-38, Gurgaon, Haryana-122001, India
Gurgaon HARYANA 122001 India
Phone
09971918887
Fax
01244834111
Email
Kuldeep.chauhan@medanta.org
Source of Monetary or Material Support
Medanta Institute of Education and Research (MIER)
Medanta-The Medicity Sector – 38, Gurgaon, Haryana- 122001, India
Primary Sponsor
Name
Medanta Institute of Education and Research MIER
Address
Medanta-The Medicity Sector – 38, Gurgaon, Haryana- 122001, India
Department of Infectious Diseases, Room No: 48, Old MHC Block, Ground Floor, Apollo Hospitals, Jubilee Hills, Hyderabad, Telangana-500096, India
Hyderabad TELANGANA
Infectious Disease Department, Block -B, 5th Floor, Apollo Speciality Hospitals, Plot No 64, Vanagaram-Ambattur Road, Ayanambakkam, Kilayanambakkam, Chennai-600095, Tamil Nadu, India Chennai TAMIL NADU
09444186807 04428296784 dskinfdis@gmail.com
Dr Reshma Tewari
Artemis Hospital
ICU-I, First Floor, Artemis Hospital, Sector-51, Gurugram-122001,
Haryana, India
Gurgaon HARYANA
B J Medical College and S G H B J Medical College and Sassoon General Hospital
Department Of Medicine,
3rd Floor, B J Medical College and S G H B J Medical College and Sassoon General Hospital
Jai Prakash Narayan Road Pune, Maharashtra - 411001 India
Pune MAHARASHTRA
09822874712 02026102312 shashisangle@yahoo.com
Dr Rahul Anil Pandit
Fortis Hospitals Limited Mulund
Intensive Care Unit, Level 2, High Dependency Unit, Department, Fortis Hospitals Limited Mulund,
Goregaon Link Road, Bhandup-West Mumbai- 400078,
Maharashtra, India
Mumbai MAHARASHTRA
Department of Pulmonology,
Lower Ground Floor,
Room No 1, Fortis Memorial Research Institute,
Sector - 44, Opposite HUDA City Centre Gurgaon, Haryana - 122002, India
Gurgaon HARYANA
Department of Respiratory,
Room No 4221,
3rd Floor,
Indraprastha Apollo Hospitals
Sarita Vihar, Delhi – Mathura Road, New Delhi – 110076, India
New Delhi DELHI
09810033395 01129871090 drchawla@hotmail.com
Dr Mohd Tariq Ali
Medanta- The Medicity
Sector -38, Gurgaon- 122001, Haryana, India Gurgaon HARYANA
09871982816
Tariq.ali@medanta.org
Dr Sushila Kataria
Medeor Hospital
Department Name- Critical Care, Room No- 84, Block No-1, Ground floor, Manesar, Gurgaon,
Haryana-122001, India
Gurgaon HARYANA
Department of pulmonology and critical care, Nayati Medicity, Near CNG Pump, NH 2,
Mathura-281001, Uttar Pradesh
And
Nayati Hospital,Near Sikandra, NH-19, Agra, UP, 2811071, India
Agra UTTAR PRADESH
09811190105 01204345509 vpcare@gmail.com
Dr Lancelot Pinto
P. D. Hinduja Hospital and Medical Research Centre
Dept of Pulmonary Medicine (PFT department)
Room no 3307
OPD building (East block), 3rd Floor, P D Hinduja National Hospital and Medical Research Centre,
Veer Savarkar Marg
Mahim, Mumbai-400016, India
Mumbai MAHARASHTRA
09820234567 024449151 lance.pinto@gmail.com
Dr Dhruva Chaudhry
Pt. B. D. Sharma Post Graduate Institute of Medical Sciences
Department of Pulmonary & Critical Care Medicine,
Emergency building, in front of ward 3, ground floor,
Pt. B. D. Sharma Post Graduate Institute of Medical Sciences, Rohtak, Haryana-124001, India
Rohtak HARYANA
09991101616
dhruvachaudhry@yahoo.co.in
Dr Vikas Agarwal
Sanjay Gandhi Post Graduate Institute of Medical Sciences
Department of Clinical Immunology & Rheumatology,
Room No 3, C block, Ground Floor, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, Uttar Pradesh 226014, India
Lucknow UTTAR PRADESH
Institutional Ethics committee P D Hinduja Hospital & Medical Research Centre
Submittted/Under Review
Institutional Ethics Committee, Fortis Memorial Research Institute
Submittted/Under Review
Institutional Ethics Committee, Pt. B.D. Sharma PGIMS/UHS
Approved
Institutional Ethics Committee, Sanjay Gandhi Post Graduate Institute of Medical Sciences
Submittted/Under Review
Institutional Ethics Committee-Apollo Research and Innovations, Jubilee Hills Apollo Health City
Submittted/Under Review
Institutional Ethics Committee-Clinical Studies Apollo Hospitals Enterprises Limited
Approved
Medanta Institutional Ethics Committee
Approved
Medanta Institutional Ethics Committee
Approved
Nayati Multi Super Specialty Institutional Ethics Committee
Submittted/Under Review
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: B972||Coronavirus as the cause of diseases classified elsewhere,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Current Standard of Care
Standard of CARE will be as per individual Hospital (Study Site) Policy
Intervention
Tocilizumab and Current Standard of Care
Dose: 6 mg/kg (up to a maximum of 480 mg), Frequency: Once, Route of Administration: Intravenous Infusion, Total duration of administration: 1 Hour and Standard of CARE will be as per individual Hospital (Study Site) Policy
Inclusion Criteria
Age From
18.00 Year(s)
Age To
85.00 Year(s)
Gender
Both
Details
I. Male or female subjects who are ≥18 years of age, on the day of signing informed consent.
II. Patient or Legally Acceptable Representative (LAR) willing to give informed Consent before study procedure.
III. Hospitalized with COVID-19 infection confirmed per WHO criteria (including a positive PCR of any specimen; e.g., respiratory, blood, urine, stool, other bodily fluid).
IV. Moderate to severe COVID 19 infection (moderate disease – increased respiratory rate 15 to 30/minute and SpO2 90%-94%; and severe disease - respiratory rate ≥ 30/minute and/or SpO2 < 90% on room air, or ARDS or Septic shock
ExclusionCriteria
Details
I. Known severe allergic reactions to TCZ or other monoclonal antibodies
II. Active tuberculosis (TB) infection.
III. Suspected or active bacterial, fungal, viral (except treated HCV or HBV infection), or other infection (besides COVID-19).
IV. In the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments.
V. Have received oral anti-rejection or immunomodulatory drugs (including TCZ) with in the past 6 months.
VI. Participating in other drug clinical trials
VII. Pregnant or breastfeeding, or positive pregnancy test in a pre-dose examination
VIII. Treatment with an investigational drug within 5 half-lives or 30 days (whichever is longer) of randomization
IX. Any serious medical condition or abnormality of clinical laboratory tests that, in the investigator’s judgment, precludes the patient safe participation in and completion of the study.
X. Definite diagnosis of rheumatic immune related diseases.
XI. Administration of steroids equivalent to methylprednisolone at a dose >1mg/kg/day) at screening/baseline
XII. Absolute Neutrophil count <500, platelet count <50,000 per microliter at screening/baseline
XIII. Alanine aminotransferase (ALT) or aspartate aminotransferase(AST) >10 times upper limit of normal detected with-in 24 hours at screening/baseline
Method of Generating Random Sequence
Permuted block randomization, fixed
Method of Concealment
On-site computer system
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
Proportion of subjects showing progressive COVID 19 disease from moderate to severe, or from severe disease to death
Up to Day 14
Secondary Outcome
Outcome
TimePoints
1.Time to clinical improvement (TTCI),defined as a National Early Warning SCORE2(NEWS2) of lesser and equal to 2, maintained for 24 hours
2.Proportion of subjects showing Improvement (≥1 grade) of CRS
3.Incidence of Mechanical Ventilation
4.Ventilator Free days to day 28
5.Organ Failure-free days to day 28
6.Incidence of Intensive Care (ICU) stay
7.Duration of ICU stay
8.ICU free days
9.Time to Clinical Improvement of COVID-19 grade
10.Mortality rate
1.Upto 28 Days
2.Upto 28 Days
3.Upto 28 Days
4.Upto Day 28
5.Upto Day 28
6.Upto 28 days
7.Upto 28 days
8.Upto 28 days
9.Upto 28 days
10.Days 7, 14, 21 and 28
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
This is a multicentric, randomized, phase III to evaluate the Clinical Outcomes and Safety of Tocilizumab (TCZ) along with standard of care in patients with cytokine release syndrome associated with moderate to severe COVID-19 infection. A total of 180 patients (90 in each arm) will be enrolled in study. The enrolment period of the study will be approximately 3 months and total duration of the study will be approximately 5 months. For an individual patient, duration of the study will be approximately 30 days, including 7 study visits. In both arms, patients will be provided the Standard of care (SOC) for COVID 19 as per the protocol of the particular hospital setup (Study site). Each patient will be monitored closely throughout his/her hospitalization for the COVID -19 and will be followed for 30 days from randomization.