OUTpatient Treatment of COVID-19 in Patients With Risk Factor for Poor Outcome (OUTCOV)

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ClinicalTrials.gov Identifier: NCT04365582

Recruitment Status : Not yet recruiting

First Posted : April 28, 2020

Last Update Posted : April 28, 2020

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Sponsor:

Information provided by (Responsible Party):

Groupe Hospitalier Paris Saint Joseph

Study Description

Brief Summary:

COVID-19 is a respiratory disease due to a novel coronavirus (SARS-CoV-2) that causes substantial morbidity and mortality. To date, no treatment has been proved to be effective in COVID-19. Elderly patients and patients with comorbidities have the worse prognosis with a higher risk of hospitalization, ICU admission and death. The efficacy of an early outpatient treatment could be suggested but need to be confirmed. This confirmation is mandatory to improve prognosis of COVID-19 but also to avoid unsuspected deleterious effect of drugs already used in clinical practice but not based on evidence.

Condition or disease	Intervention/treatment	Phase
COVID	Drug: Azithromycin Drug: Hydroxychloroquine Drug: Lopinavir 200Mg/Ritonavir 50Mg Tab	Phase 3

Detailed Description:

The investigators make the hypothesis that an early outpatient treatment of COVID among patient with respiratory symptoms and risk factors for poor outcome can improve the prognosis of these patient and decrease the need for hospital admission.

Our study is an open label randomized clinical trial comparing 4 arms of treatment: Standards of Care (SoC) alone versus SoC + Azithromycine versus SoC + Hydroxychloroquine vs Soc + Lopinavir/Ritonavir.

Our involved population is patients more than 50 years of age with comorbidity or patients more than 70 years of age.

Our primary objective is to evaluate the efficacy of early outpatient treatment compared to standard of care in patients COVID-19 with risk factors for poor outcome. The criteria is hospital admission at Day 20 and the hospital admission rate will be compared between groups by a Chi² test or a Fisher's exact test.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	640 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Randomized Trial of Efficacy and Safety of an Early OUTpatient Treatment of COVID-19 in Patients With Risk Factor for Poor Outcome: a Strategy to Prevent Hospitalization
Estimated Study Start Date :	April 28, 2020
Estimated Primary Completion Date :	July 28, 2020
Estimated Study Completion Date :	January 28, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Ritonavir Lopinavir

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Azithromycin Azithromycin	Drug: Azithromycin 500 mg day 1 ; 250 mg/day for 4 days
Experimental: Hydroxychlororquine Hydroxychlororquine	Drug: Hydroxychloroquine 200 mg x 3/day for 10 days
Experimental: Lopinavir/Ritonavir Lopinavir/Ritonavir	Drug: Lopinavir 200Mg/Ritonavir 50Mg Tab 400/100 mg (2 tablets) x 2/day for 15 days Other Name: Lopinavir/Ritonavir
No Intervention: standards of care SoC

Outcome Measures

Primary Outcome Measures :

Hospital admission [ Time Frame: Day 20 ]
Hospitalization at D20

Secondary Outcome Measures :

Effect of treatment on Death at D20 [ Time Frame: Day 20 ]
This outcome corresponds to the number of patients who died on day 20.
Effect of treatment on Death at D60 [ Time Frame: Day 60 ]
This outcome corresponds to the number of patients who died on day 60.
Effect of treatment on Death due to COVID at D20 [ Time Frame: Day 20 ]
This outcome corresponds to the number of patients who died due to COVID on day 20.
Effect of treatment on Death due to COVID at D60 [ Time Frame: Day 60 ]
This outcome corresponds to the number of patients who died due to COVID on day 60.
Effect of treatment on need for ICU stay at D20 [ Time Frame: Day 20 ]
This outcome corresponds to the number of participants who need ICU stay at day 20.
Effect of treatment on need for ICU stay at D60 [ Time Frame: Day 60 ]
This outcome corresponds to the number of participants who need ICU stay at day 60.
Effect of treatment on duration of ICU stay at D20 [ Time Frame: Day 20 ]
This outcome evaluates the duration of patient's ICU stay at day 20.
Effect of treatment on duration of ICU stay at D60 [ Time Frame: Day 60 ]
This outcome evaluates the duration of patient's ICU stay at day 60.
Effect of treatment on need of mechanical ventilation at D20 [ Time Frame: Day 20 ]
This outcome corresponds to the number of participants who need mechanical ventilation at D20.
Effect of treatment on need of mechanical ventilation at D60 [ Time Frame: Day 60 ]
This outcome corresponds to the number of participants who need mechanical ventilation at D60.
Effect of treatment on duration of mechanical ventilation at D20 [ Time Frame: Day 20 ]
This outcome corresponds to the duration of patient's mechanical ventilation at D20.
Effect of treatment on duration of mechanical ventilation at D60 [ Time Frame: Day 60 ]
This outcome corresponds to the duration of patient's mechanical ventilation at D60.
Effect of treatment on time to hospitalization at D20 [ Time Frame: Day 20 ]
This outcome evaluates the delay between inclusion and hospitalization at D20.
Effect of treatment on time to hospitalization at D60 [ Time Frame: Day 60 ]
This outcome evaluates the delay between inclusion and hospitalization at D60.
Effect of treatment on Duration of Hospital stay et D20 [ Time Frame: Day 20 ]
This outcome evaluates the duration of patient's Hospital stay at D20.
Effect of treatment on Duration of Hospital stay et D60 [ Time Frame: Day 60 ]
This outcome evaluates the duration of patient's Hospital stay at D60.
Effect of treatment on Duration of symptoms at D20 [ Time Frame: Day 20 ]
This outcome evaluates the duration of symptoms at D20 after treatment.
Effect of treatment on Duration of symptoms at D60 [ Time Frame: Day 60 ]
This outcome evaluates the duration of symptoms at D60 after treatment.
Incidence of Treatment-Emergent Adverse Events [ Time Frame: Month 6 ]
This outcome measures the number of participants with treatment-related adverse events as assessed by CTCAE v4.0, at the end of study.

Other Outcome Measures:

Effect of treatment on chest radiological features [ Time Frame: Month 6 ]
This outcome evaluates the chest radiological features on Chest HRCT, at 6 months, after treatment.
Effect of treatment on respiratory capacity [ Time Frame: Month 6 ]
This outcome evaluates the Pulmonary function test at 6 month, after treatment.
Cost consequence analysis [ Time Frame: Month 6 ]
This ouctome eavaluates costs and consequences which will be presented for each stakeholder in a disaggregated way at the end of study.

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	50 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Either patients over 50 years of age with at least one comorbidity (hypertension, diabetes, obesity, cancer, chronic renal disease, immunodeficiency) OR patients over 70 years of age with or without comorbidity
Laboratory (PCR-) proved infection by COVID-19 or radiological sign highly suggestive of COVID-19
Respiratory symptoms (cough, chest discomfort, dyspnea)
Affiliation to the social security network
Able to understand and sign a written informed consent form

Exclusion Criteria:

Need for hospitalization according to updated French guidelines (ministère de la santé_04/04/2020)
Patient in long-term care facility
Patient without concern confirmation of COVID-19 by laboratory (PCR swab) test or chest CT
Known hypersensitivity or contra-indication to the 3 experimental treatments (azithromycin, hydroxychloroquine, lopinavir/ritonavir).
Any reason making follow up of the patient impossible during the study period.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04365582

Contacts

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Contact: Helene Beaussier, MD PhD	1.44.12.78.83 ext 00 33	hbeaussier@hpsj.fr

Locations

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France
Hôpital Privé d'Antony
Antony, France, 92160
Contact: Jean Marc NACCACHE, MD
Principal Investigator: Jean Marc NACCACHE, MD
Hôpital Avicenne
Bobigny, France, 93000
Contact: Hilario Nunes, MD hilario.nunes@aphp.fr
Principal Investigator: Hilario Nunes, MD
Centre Hospitalier Intercommunal de Créteil
Créteil, France
Contact: Christos CHOUAID, MD christos.chouaid@chicreteil.fr
Principal Investigator: Christos CHOUAID, MD
Groupe Hospitalier Paris Saint-Joseph
Paris, France, 75014
Contact: Jean-Marc Naccache, MD 1 44 12 67 47 ext 00 33 jmnaccache@hpsj.fr
Institut Mutualiste Montsouris
Paris, France, 75014
Contact: Pierre CHARLES, MD Pierre.charles@imm.fr
Principal Investigator: Pierre CHARLES, MD

Sponsors and Collaborators

Groupe Hospitalier Paris Saint Joseph

Investigators

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Principal Investigator:	Jean-Marc Naccache, MD	Groupe Hospitalier Paris Saint Joseph

More Information

Publications:

Guan WJ, Liang WH, Zhao Y, Liang HR, Chen ZS, Li YM, Liu XQ, Chen RC, Tang CL, Wang T, Ou CQ, Li L, Chen PY, Sang L, Wang W, Li JF, Li CC, Ou LM, Cheng B, Xiong S, Ni ZY, Xiang J, Hu Y, Liu L, Shan H, Lei CL, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Cheng LL, Ye F, Li SY, Zheng JP, Zhang NF, Zhong NS, He JX; China Medical Treatment Expert Group for COVID-19. Comorbidity and its impact on 1590 patients with COVID-19 in China: a nationwide analysis. Eur Respir J. 2020 May 14;55(5). pii: 2000547. doi: 10.1183/13993003.00547-2020. Print 2020 May.

Khan AA, Slifer TR, Araujo FG, Remington JS. Effect of clarithromycin and azithromycin on production of cytokines by human monocytes. Int J Antimicrob Agents. 1999 Feb;11(2):121-32.

Cortegiani A, Ingoglia G, Ippolito M, Giarratano A, Einav S. A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19. J Crit Care. 2020 Mar 10. pii: S0883-9441(20)30390-7. doi: 10.1016/j.jcrc.2020.03.005. [Epub ahead of print]

Chan JF, Yao Y, Yeung ML, Deng W, Bao L, Jia L, Li F, Xiao C, Gao H, Yu P, Cai JP, Chu H, Zhou J, Chen H, Qin C, Yuen KY. Treatment With Lopinavir/Ritonavir or Interferon-β1b Improves Outcome of MERS-CoV Infection in a Nonhuman Primate Model of Common Marmoset. J Infect Dis. 2015 Dec 15;212(12):1904-13. doi: 10.1093/infdis/jiv392. Epub 2015 Jul 21.

Keyaerts E, Vijgen L, Maes P, Neyts J, Van Ranst M. In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine. Biochem Biophys Res Commun. 2004 Oct 8;323(1):264-8.

Rolain JM, Colson P, Raoult D. Recycling of chloroquine and its hydroxyl analogue to face bacterial, fungal and viral infections in the 21st century. Int J Antimicrob Agents. 2007 Oct;30(4):297-308. Epub 2007 Jul 16. Review.

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]

Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z, Hu Z, Zhong W, Xiao G. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020 Mar;30(3):269-271. doi: 10.1038/s41422-020-0282-0. Epub 2020 Feb 4.

Nukoolkarn V, Lee VS, Malaisree M, Aruksakulwong O, Hannongbua S. Molecular dynamic simulations analysis of ritonavir and lopinavir as SARS-CoV 3CL(pro) inhibitors. J Theor Biol. 2008 Oct 21;254(4):861-7. doi: 10.1016/j.jtbi.2008.07.030. Epub 2008 Jul 29.

Young BE, Ong SWX, Kalimuddin S, Low JG, Tan SY, Loh J, Ng OT, Marimuthu K, Ang LW, Mak TM, Lau SK, Anderson DE, Chan KS, Tan TY, Ng TY, Cui L, Said Z, Kurupatham L, Chen MI, Chan M, Vasoo S, Wang LF, Tan BH, Lin RTP, Lee VJM, Leo YS, Lye DC; Singapore 2019 Novel Coronavirus Outbreak Research Team. Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore. JAMA. 2020 Mar 3. doi: 10.1001/jama.2020.3204. [Epub ahead of print]

Metlay JP, Waterer GW, Long AC, Anzueto A, Brozek J, Crothers K, Cooley LA, Dean NC, Fine MJ, Flanders SA, Griffin MR, Metersky ML, Musher DM, Restrepo MI, Whitney CG. Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-e67. doi: 10.1164/rccm.201908-1581ST.

Yogasundaram H, Putko BN, Tien J, Paterson DI, Cujec B, Ringrose J, Oudit GY. Hydroxychloroquine-induced cardiomyopathy: case report, pathophysiology, diagnosis, and treatment. Can J Cardiol. 2014 Dec;30(12):1706-15. doi: 10.1016/j.cjca.2014.08.016. Epub 2014 Aug 23. Review.

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Responsible Party:	Groupe Hospitalier Paris Saint Joseph
ClinicalTrials.gov Identifier:	NCT04365582
Other Study ID Numbers:	OUTCOV
First Posted:	April 28, 2020 Key Record Dates
Last Update Posted:	April 28, 2020
Last Verified:	April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

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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

Keywords provided by Groupe Hospitalier Paris Saint Joseph:


COVID outpatient ambulatory prognosis

Additional relevant MeSH terms:

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Ritonavir Lopinavir Azithromycin Hydroxychloroquine HIV Protease Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents	Antiviral Agents Anti-Infective Agents Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors Anti-Bacterial Agents Antimalarials Antiprotozoal Agents Antiparasitic Agents Antirheumatic Agents

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