AzTrials
AzTrials

COVIDPhase 3OUTCOVNCT04365582

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

A Phase 3 study testing Azithromycin, Hydroxychloroquine and Lopinavir 200Mg/Ritonavir 50Mg Tab in people with COVID, run by Fondation Hôpital Saint-Joseph.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 50 years and older
Conditions the study is for
COVID
What is being tested?
Azithromycin, Hydroxychloroquine and Lopinavir 200Mg/Ritonavir 50Mg Tab
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
7 May 2020to 19 Apr 2021
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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.

About this study

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

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.

Read the 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.

Conditions
COVID
Being tested
Azithromycin, Hydroxychloroquine, Lopinavir 200Mg/Ritonavir 50Mg Tab
Keywords
COVID, outpatient, ambulatory, prognosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AzithromycinDrug

    500 mg day 1 ; 250 mg/day for 4 days

  • HydroxychloroquineDrug

    200 mg x 3/day for 10 days

  • Lopinavir 200Mg/Ritonavir 50Mg TabDrug

    Also called Lopinavir/Ritonavir

    400/100 mg (2 tablets) x 2/day for 15 days

Study groups in NCT04365582
Study groupRoleWhat they receive
AzithromycinExperimentalAzithromycin
Receives: Drug: Azithromycin
HydroxychlororquineExperimentalHydroxychlororquine
Receives: Drug: Hydroxychloroquine
Lopinavir/RitonavirExperimentalLopinavir/Ritonavir
Receives: Drug: Lopinavir 200Mg/Ritonavir 50Mg Tab
standards of careNo interventionSoC

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Hospital admission

    Hospitalization at D20

    Measured: Day 20

Secondary outcomes (19)

  1. Effect of treatment on Death at D20

    This outcome corresponds to the number of patients who died on day 20.

    Measured: Day 20

  2. Effect of treatment on Death at D60

    This outcome corresponds to the number of patients who died on day 60.

    Measured: Day 60

  3. Effect of treatment on Death due to COVID at D20

    This outcome corresponds to the number of patients who died due to COVID on day 20.

    Measured: Day 20

  4. Effect of treatment on Death due to COVID at D60

    This outcome corresponds to the number of patients who died due to COVID on day 60.

    Measured: Day 60

  5. Effect of treatment on need for ICU stay at D20

    This outcome corresponds to the number of participants who need ICU stay at day 20.

    Measured: Day 20

  6. Effect of treatment on need for ICU stay at D60

    This outcome corresponds to the number of participants who need ICU stay at day 60.

    Measured: Day 60

  7. Effect of treatment on duration of ICU stay at D20

    This outcome evaluates the duration of patient's ICU stay at day 20.

    Measured: Day 20

  8. Effect of treatment on duration of ICU stay at D60

    This outcome evaluates the duration of patient's ICU stay at day 60.

    Measured: Day 60

  9. Effect of treatment on need of mechanical ventilation at D20

    This outcome corresponds to the number of participants who need mechanical ventilation at D20.

    Measured: Day 20

  10. Effect of treatment on need of mechanical ventilation at D60

    This outcome corresponds to the number of participants who need mechanical ventilation at D60.

    Measured: Day 60

  11. Effect of treatment on duration of mechanical ventilation at D20

    This outcome corresponds to the duration of patient's mechanical ventilation at D20.

    Measured: Day 20

  12. Effect of treatment on duration of mechanical ventilation at D60

    This outcome corresponds to the duration of patient's mechanical ventilation at D60.

    Measured: Day 60

  13. Effect of treatment on time to hospitalization at D20

    This outcome evaluates the delay between inclusion and hospitalization at D20.

    Measured: Day 20

  14. Effect of treatment on time to hospitalization at D60

    This outcome evaluates the delay between inclusion and hospitalization at D60.

    Measured: Day 60

  15. Effect of treatment on Duration of Hospital stay et D20

    This outcome evaluates the duration of patient's Hospital stay at D20.

    Measured: Day 20

  16. Effect of treatment on Duration of Hospital stay et D60

    This outcome evaluates the duration of patient's Hospital stay at D60.

    Measured: Day 60

  17. Effect of treatment on Duration of symptoms at D20

    This outcome evaluates the duration of symptoms at D20 after treatment.

    Measured: Day 20

  18. Effect of treatment on Duration of symptoms at D60

    This outcome evaluates the duration of symptoms at D60 after treatment.

    Measured: Day 60

  19. Incidence of Treatment-Emergent Adverse Events

    This outcome measures the number of participants with treatment-related adverse events as assessed by CTCAE v4.0, at the end of study.

    Measured: Month 6

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Apr 2020
  2. Study start7 May 2020
  3. Primary completion31 Dec 2020
  4. Study completion19 Apr 2021

Why it stopped: The PI decided.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04365582
Sponsor's protocol ID
OUTCOV
Acronym
OUTCOV
Status last verified
Apr 2020
First submitted
23 Apr 2020
Last updated
27 Apr 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

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):2000547. doi: 10.1183/13993003.00547-2020. Print 2020 May.

    PubMed 32217650

  • 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. doi: 10.1016/s0924-8579(98)00091-0.

    PubMed 10221415

  • 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 Jun;57:279-283. doi: 10.1016/j.jcrc.2020.03.005. Epub 2020 Mar 10.

    PubMed 32173110

  • 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-beta1b 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.

    PubMed 26198719

  • 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. doi: 10.1016/j.bbrc.2004.08.085.

    PubMed 15351731

  • 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. doi: 10.1016/j.ijantimicag.2007.05.015. Epub 2007 Jul 16.

    PubMed 17629679

  • Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, Doudier B, Courjon J, Giordanengo V, Vieira VE, Tissot Dupont H, Honore S, Colson P, Chabriere E, La Scola B, Rolain JM, Brouqui P, Raoult D. RETRACTED: Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020 Jul;56(1):105949. doi: 10.1016/j.ijantimicag.2020.105949. Epub 2020 Mar 20.

    PubMed 32205204

  • 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. No abstract available.

    PubMed 32020029

  • 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.

    PubMed 18706430

  • 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 Apr 21;323(15):1488-1494. doi: 10.1001/jama.2020.3204.

    PubMed 32125362

  • 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.

    PubMed 31573350

  • 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.

    PubMed 25475472

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Azithromycin, Hydroxychloroquine and Lopinavir 200Mg/Ritonavir 50Mg Tab in people with COVID, run by Fondation Hôpital Saint-Joseph.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 27 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Hospital admission (time frame: Day 20). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04365582, which also lists 12 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2021.

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