Prophylactic Corticosteroid to Prevent COVID-19 Cytokine Storm

Covid-19 Clinical Trial

Official title:

Prophylactic Corticosteroid to Prevent COVID-19 Cytokine Storm

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04355247
• Other study ID #: CCAM 20-01
• Status: Recruiting
• Phase: Phase 2
• Start date: April 14, 2020
• Est. completion date: April 30, 2021

Study information

• Verified date: April 2020
• Source: Auxilio Mutuo Cancer Center
• Contact: Fernando Cabanillas, MD
• Phone: 787-758-2000
• Email: cabanillasmd[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase II pilot exploratory study designed to investigate if prophylactic treatment with short term steroids administered to high risk Covid-19 patient might prevent cytokine storm and progression to respiratory failure. High risk is defined based on serologic markers of inflammation that include abnormalities of Interleukin 6 (IL-6), Ferritin , D-dimer, Lactate Dehydrogenase (LDH), as well as lymphopenia and impaired O2 saturation prior to or on the 7th day of first symptom of Covid-19.

Description:

To decrease the rate of progression to hypoxemic respiratory failure in high risk patients with Covid-19, treated with prophylactic steroids during the first phase of the disease.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: April 30, 2021
• Est. primary completion date: July 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• All patients diagnosed with Covid-19 will be registered on the study regardless pf their severity, but only those who meet high risk criteria will be treated with steroids. Those who don't meet the criteria will only be registered with no need to collect further data except baseline labs and CT Chest. They should sign the consent form and the data manager can collect the rest of the information.

• Patients older than 18 years diagnosed with Covid-19 by Polymerase Chain Reaction (PCR) or by rapid serological test will be eligible. Cases who are Immunoglobulin G (IgG) positive but Immunoglobulin M (IgM) negative, will not be considered eligible unless they are positive for molecular PCR test. Eligible patients will be registered on study on or before 7 days from first onset of symptoms.

Exclusion Criteria:

• Any patient with life expectancy < 1 month

• Any patient who is oxygen dependent

• Any patient with long standing history of severe Chronic Obstructive Pulmonary Disease (COPD)

• Any patient who is chronically oxygen dependent because of previous existing lung disease

• Anyone with severely uncontrolled diabetes despite adequate management

• Anyone with active serious bacterial infection such as septicemia or pneumonia

• Anyone receiving Tocilizumab (anti IL-6 therapy) or plasma therapy

• Any patient already receiving steroids from another pre-existing illness

Related Conditions & MeSH terms

• Covid-19

Intervention

Drug:
• MethylPREDNISolone 80 Mg/mL Injectable Suspension
Patients will be admitted to a regular room in the hospital (not ICU) They will be monitored closely with vital signs every 4 hours to ensure their respiratory and cardiovascular status do not deteriorate. Methylprednisolone 80 mg IV bolus injection will be given daily x 5 days starting upon day 1 of admission to hospital.

Locations

Country	Name	City	State
Puerto Rico	Hospital Auxilio Mutuo Cancer Center	San Juan
Puerto Rico	San Juan City Hospital / Puerto Rico Medical Center	San Juan

Sponsors (1)

Lead Sponsor	Collaborator
Auxilio Mutuo Cancer Center

Country where clinical trial is conducted

Puerto Rico, 

References & Publications (8)

Carr AC. A new clinical trial to test high-dose vitamin C in patients with COVID-19. Crit Care. 2020 Apr 7;24(1):133. doi: 10.1186/s13054-020-02851-4. — View Citation

Chen L, Xiong J, Bao L, Shi Y. Convalescent plasma as a potential therapy for COVID-19. Lancet Infect Dis. 2020 Apr;20(4):398-400. doi: 10.1016/S1473-3099(20)30141-9. Epub 2020 Feb 27. — View Citation

Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, Doudier B, Courjon J, Giordanengo V, Vieira VE, Dupont HT, Honoré S, Colson P, Chabrière E, La Scola B, Rolain JM, Brouqui P, Raoult D. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020 Mar 20:105949. doi: 10.1016/j.ijantimicag.2020.105949. [Epub ahead of print] — View Citation

Grein J, Ohmagari N, Shin D, Diaz G, Asperges E, Castagna A, Feldt T, Green G, Green ML, Lescure FX, Nicastri E, Oda R, Yo K, Quiros-Roldan E, Studemeister A, Redinski J, Ahmed S, Bernett J, Chelliah D, Chen D, Chihara S, Cohen SH, Cunningham J, D'Arminio Monforte A, Ismail S, Kato H, Lapadula G, L'Her E, Maeno T, Majumder S, Massari M, Mora-Rillo M, Mutoh Y, Nguyen D, Verweij E, Zoufaly A, Osinusi AO, DeZure A, Zhao Y, Zhong L, Chokkalingam A, Elboudwarej E, Telep L, Timbs L, Henne I, Sellers S, Cao H, Tan SK, Winterbourne L, Desai P, Mera R, Gaggar A, Myers RP, Brainard DM, Childs R, Flanigan T. Compassionate Use of Remdesivir for Patients with Severe Covid-19. N Engl J Med. 2020 Apr 10. doi: 10.1056/NEJMoa2007016. [Epub ahead of print] — View Citation

Russell CD, Millar JE, Baillie JK. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet. 2020 Feb 15;395(10223):473-475. doi: 10.1016/S0140-6736(20)30317-2. Epub 2020 Feb 7. — View Citation

Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, Huang H, Zhang L, Zhou X, Du C, Zhang Y, Song J, Wang S, Chao Y, Yang Z, Xu J, Zhou X, Chen D, Xiong W, Xu L, Zhou F, Jiang J, Bai C, Zheng J, Song Y. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med. 2020 Mar 13. doi: 10.1001/jamainternmed.2020.0994. [Epub ahead of print] — View Citation

Zhang C, Wu Z, Li JW, Zhao H, Wang GQ. The cytokine release syndrome (CRS) of severe COVID-19 and Interleukin-6 receptor (IL-6R) antagonist Tocilizumab may be the key to reduce the mortality. Int J Antimicrob Agents. 2020 Mar 29:105954. doi: 10.1016/j.ijantimicag.2020.105954. [Epub ahead of print] — View Citation

Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062. doi: 10.1016/S0140-6736(20)30566-3. Epub 2020 Mar 11. Erratum in: Lancet. 2020 Mar 28;395(10229):1038. Lancet. 2020 Mar 28;395(10229):1038. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical complete response criteria	Clinical complete response criteria requires all the following: No need for ventilatory support at any point; O2 Saturation of >/= 93% by day 14 of therapy; Alive by day 28 from registration; CT chest with minimal or no evidence of disease by day 28 from registration	14 days
Primary	Clinical Partial Response criteria	Clinical Partial Response criteria require that 2 of the following be present by day 14 of therapy: No need for ventilatory support at any point O2 saturation > 93% bay day 14 from registration; CT chest stable to improve over baseline by day 28 from registration	14 days
Secondary	Secondary response criteria	Decrease of at least 25% in anyone of the following markers: IL-6, Ferritin, D-dimer, C reactive protein (CRP) or LDH by day 14; - Improvement of absolute lymphocyte count in those presenting with lymphopenia. Improvement is defined as increase by 25% or more by day 14.	14 days

External Links

•   Level of IL-6 predicts respiratory failure in hospitalized symptomatic COVID-19 patients
•   The potential role of IL-6 in monitoring severe case of coronavirus disease 2019