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The PI decided.
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Azithromycin | Experimental | Azithromycin |
|
| Hydroxychlororquine | Experimental | Hydroxychlororquine |
|
| Lopinavir/Ritonavir | Experimental | Lopinavir/Ritonavir |
|
| standards of care | No Intervention | SoC |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Azithromycin | Drug | 500 mg day 1 ; 250 mg/day for 4 days |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Hospital admission | Hospitalization at D20 | Day 20 |
| Measure | Description | Time Frame |
|---|---|---|
| Effect of treatment on Death at D20 | This outcome corresponds to the number of patients who died on day 20. | Day 20 |
| Effect of treatment on Death at D60 | This outcome corresponds to the number of patients who died on day 60. |
| Measure | Description | Time Frame |
|---|---|---|
| Effect of treatment on chest radiological features | This outcome evaluates the chest radiological features on Chest HRCT, at 6 months, after treatment. | Month 6 |
| Effect of treatment on respiratory capacity |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jean-Marc Naccache, MD | Fondation Hôpital Saint-Joseph | Principal Investigator |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32217650 | Background | 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. | |
| 10221415 |
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| ID | Term |
|---|---|
| D017963 | Azithromycin |
| D006886 | Hydroxychloroquine |
| D061466 | Lopinavir |
| D019438 | Ritonavir |
| ID | Term |
|---|---|
| D004917 | Erythromycin |
| D018942 | Macrolides |
| D061065 | Polyketides |
| D007783 | Lactones |
| D009930 |
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| Hydroxychloroquine |
| Drug |
200 mg x 3/day for 10 days |
|
| Lopinavir 200Mg/Ritonavir 50Mg Tab | Drug | 400/100 mg (2 tablets) x 2/day for 15 days |
|
|
| Day 60 |
| 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. | Day 20 |
| 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. | Day 60 |
| 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. | Day 20 |
| 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. | Day 60 |
| Effect of treatment on duration of ICU stay at D20 | This outcome evaluates the duration of patient's ICU stay at day 20. | Day 20 |
| Effect of treatment on duration of ICU stay at D60 | This outcome evaluates the duration of patient's ICU stay at day 60. | Day 60 |
| Effect of treatment on need of mechanical ventilation at D20 | This outcome corresponds to the number of participants who need mechanical ventilation at D20. | Day 20 |
| Effect of treatment on need of mechanical ventilation at D60 | This outcome corresponds to the number of participants who need mechanical ventilation at D60. | Day 60 |
| Effect of treatment on duration of mechanical ventilation at D20 | This outcome corresponds to the duration of patient's mechanical ventilation at D20. | Day 20 |
| Effect of treatment on duration of mechanical ventilation at D60 | This outcome corresponds to the duration of patient's mechanical ventilation at D60. | Day 60 |
| Effect of treatment on time to hospitalization at D20 | This outcome evaluates the delay between inclusion and hospitalization at D20. | Day 20 |
| Effect of treatment on time to hospitalization at D60 | This outcome evaluates the delay between inclusion and hospitalization at D60. | Day 60 |
| Effect of treatment on Duration of Hospital stay et D20 | This outcome evaluates the duration of patient's Hospital stay at D20. | Day 20 |
| Effect of treatment on Duration of Hospital stay et D60 | This outcome evaluates the duration of patient's Hospital stay at D60. | Day 60 |
| Effect of treatment on Duration of symptoms at D20 | This outcome evaluates the duration of symptoms at D20 after treatment. | Day 20 |
| Effect of treatment on Duration of symptoms at D60 | This outcome evaluates the duration of symptoms at D60 after treatment. | Day 60 |
| 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. | Month 6 |
This outcome evaluates the Pulmonary function test at 6 month, after treatment.
| Month 6 |
| Cost consequence analysis | This ouctome eavaluates costs and consequences which will be presented for each stakeholder in a disaggregated way at the end of study. | Month 6 |
| Background |
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| 32173110 | Background | 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. |
| 26198719 | Background | 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. |
| 15351731 | Background | 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. |
| 17629679 | Background | 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. |
| 32205204 | Background | 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. |
| 32020029 | Background | 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. |
| 18706430 | Background | 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. |
| 32125362 | Background | 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. |
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| 25475472 | Background | 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. |
| Organic Chemicals |
| D002738 | Chloroquine |
| D000634 | Aminoquinolines |
| D011804 | Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D001393 | Azoles |