Hydroxychloroquine With or Without Azithromycin for Virologic Cure of COVID-19

NCT04349592 | Completed DMC

• 1 other identifier: MRC-05-001
• Study Type: interventional
• Target: 456
• Locations: 1 country
• Sites: 1

Brief Summary

Q-PROTECT is a placebo controlled randomized trial (RCT) to ascertain the efficacy of hydroxychloroquine (HC) alone or, in combination with azithromycin (AZ), in reducing viral load in patients with COVID 19.

Conditions

Covid19

Keywords

Covid19; Qatar; Coronavirus; Hydroxychloroquine; Respiratory disease; Pandemic; Azithromycin; Viral Load; Emergency Department; SARS-CoV-2

Outcome Measures

Primary Outcomes (1)

• Proportion of virologically cured (PCR-negative status) as assessed on day six

  Days

  Day 6

Secondary Outcomes (5)

• virologic cure on other study days

  Day14 and Day 21

• virologic semiquantitative analysis of changing viral load

  Day 1 to Day 21

• proportion of initially symtomatic subjects with disappearance of clinical symptoms

  Day14 and Day 21

• proportion of initially asymtomatic subjects with appearance of new clinical symptoms

  Day14 and Day 21

• proportions of subjects with potentially medication- related adverse events

  7 day

Study Arms (3)

Combination therapy group

EXPERIMENTAL

hydroxychloroquine 200mg TID for 7 days plus Azithromycin 500mg OD 1st day and 250 from day 2 to 5

Drug: Hydroxychloroquine; Drug: Azithromycin

Monotherapy therapy group

ACTIVE COMPARATOR

hydroxychloroquine 200mg TID for 7 days plus Placebo 1 tab OD 1st day and 1 tab from day 2 to 5

Drug: Hydroxychloroquine; Other: Placebo capsules

Control group

PLACEBO COMPARATOR

Placebo Cap TID for 7 days plus Placebo 1 tab OD 1st day and 1 tab from day 2 to 5

Other: Placebo Tablet; Other: Placebo capsules

Interventions

Hydroxychloroquine DRUG

Hydroxychloroquine 200 mg tablet oral, one tablet three times a day for 7 days

Also known as: Plaquenil,

Combination therapy group; Monotherapy therapy group

Azithromycin DRUG

Azithromycin 250 mg capsules oral, 2 capsules on day one, followed by 1 capsule once a day for days 2-5.

Also known as: Zithromax, Azithrocin

Combination therapy group

Placebo Tablet OTHER

Oral, one tablet three times a day for 7 days

Control group

Placebo capsules OTHER

Oral 2 capsules on day one, followed by 1 capsule once a day for days 2-5.

Control group; Monotherapy therapy group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient is in HMC facility for low-acuity, Covid-positive patients being quarantined.
• Positive Covid test on qualitative assay used during routine care (i.e. not as part of Q-PROTECT)
• Age at least 18

You may not qualify if:

• Treating physician judges patient not appropriate for study participation for any reason
• Age \<18
• Breastfeeding or pregnancy (patient-reported pregnancy status is sufficient)
• Hypersensitivity to chloroquine or HC or AZ
• History of or known QT prolongation
• EKG required before study entry and on each visit during the subject's first seven days on pro-tocol, during the time period HC is being taken
• Baseline QTc \>480 if QRS width normal; QTc \>510 if QRS \>120
• Known G6PD deficiency, porphyria, or retinopathy (eye exam prior to study entry)
• Known hepatic or renal disease (or abnormality on liver or renal function testing at study day 1)
• Low magnesium or low potassium (by testing on day 1)
• Current (pre-study) therapy with antimalarial or dapsone
• Current (pre-study) therapy with antiviral agents (e.g. oseltamivir)
• Tisdale36 score exceeding 6 as tallied below (based on ACC recommendations)\*
• point each: age\>67, female sex, or being on loop diuretic
• points each: serum potassium \<3.6, QTc\>449, acute myocardial infarction

Sponsors & Collaborators

• Hamad Medical Corporation: lead

Study Sites (1)

Hamad Medical Corporation

Doha, 3050, Qatar

Location

Related Publications (37)

• Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R, Niu P, Zhan F, Ma X, Wang D, Xu W, Wu G, Gao GF, Tan W; China Novel Coronavirus Investigating and Research Team. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020 Feb 20;382(8):727-733. doi: 10.1056/NEJMoa2001017. Epub 2020 Jan 24.

  PMID: 31978945 BACKGROUND

• Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, Xia J, Yu T, Zhang X, Zhang L. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020 Feb 15;395(10223):507-513. doi: 10.1016/S0140-6736(20)30211-7. Epub 2020 Jan 30.

  PMID: 32007143 BACKGROUND

• Xu Z, Li S, Tian S, Li H, Kong LQ. Full spectrum of COVID-19 severity still being depicted. Lancet. 2020 Mar 21;395(10228):947-948. doi: 10.1016/S0140-6736(20)30308-1. Epub 2020 Feb 14. No abstract available.

  PMID: 32066525 BACKGROUND

• Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, Liu S, Zhao P, Liu H, Zhu L, Tai Y, Bai C, Gao T, Song J, Xia P, Dong J, Zhao J, Wang FS. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020 Apr;8(4):420-422. doi: 10.1016/S2213-2600(20)30076-X. Epub 2020 Feb 18. No abstract available.

  PMID: 32085846 BACKGROUND

• Xu XW, Wu XX, Jiang XG, Xu KJ, Ying LJ, Ma CL, Li SB, Wang HY, Zhang S, Gao HN, Sheng JF, Cai HL, Qiu YQ, Li LJ. Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series. BMJ. 2020 Feb 19;368:m606. doi: 10.1136/bmj.m606.

  PMID: 32075786 BACKGROUND

• Van Cuong L, Giang HTN, Linh LK, Shah J, Van Sy L, Hung TH, Reda A, Truong LN, Tien DX, Huy NT. The first Vietnamese case of COVID-19 acquired from China. Lancet Infect Dis. 2020 Apr;20(4):408-409. doi: 10.1016/S1473-3099(20)30111-0. Epub 2020 Feb 19. No abstract available.

  PMID: 32085849 BACKGROUND

• Wang CJ, Ng CY, Brook RH. Response to COVID-19 in Taiwan: Big Data Analytics, New Technology, and Proactive Testing. JAMA. 2020 Apr 14;323(14):1341-1342. doi: 10.1001/jama.2020.3151. No abstract available.

  PMID: 32125371 BACKGROUND

• Adalja AA, Toner E, Inglesby TV. Priorities for the US Health Community Responding to COVID-19. JAMA. 2020 Apr 14;323(14):1343-1344. doi: 10.1001/jama.2020.3413. No abstract available.

  PMID: 32125355 BACKGROUND

• Anderson M, Mckee M, Mossialos E. Covid-19 exposes weaknesses in European response to outbreaks. BMJ. 2020 Mar 18;368:m1075. doi: 10.1136/bmj.m1075. No abstract available.

  PMID: 32188590 BACKGROUND

• Chatterjee P. Indian pharma threatened by COVID-19 shutdowns in China. Lancet. 2020 Feb 29;395(10225):675. doi: 10.1016/S0140-6736(20)30459-1. No abstract available.

  PMID: 32113494 BACKGROUND

• Mahase E. Covid-19: WHO declares pandemic because of "alarming levels" of spread, severity, and inaction. BMJ. 2020 Mar 12;368:m1036. doi: 10.1136/bmj.m1036. No abstract available.

  PMID: 32165426 BACKGROUND

• Wong JEL, Leo YS, Tan CC. COVID-19 in Singapore-Current Experience: Critical Global Issues That Require Attention and Action. JAMA. 2020 Apr 7;323(13):1243-1244. doi: 10.1001/jama.2020.2467. No abstract available.

  PMID: 32077901 BACKGROUND

• Holshue ML, DeBolt C, Lindquist S, Lofy KH, Wiesman J, Bruce H, Spitters C, Ericson K, Wilkerson S, Tural A, Diaz G, Cohn A, Fox L, Patel A, Gerber SI, Kim L, Tong S, Lu X, Lindstrom S, Pallansch MA, Weldon WC, Biggs HM, Uyeki TM, Pillai SK; Washington State 2019-nCoV Case Investigation Team. First Case of 2019 Novel Coronavirus in the United States. N Engl J Med. 2020 Mar 5;382(10):929-936. doi: 10.1056/NEJMoa2001191. Epub 2020 Jan 31.

  PMID: 32004427 BACKGROUND

• Mahase E. Covid-19: UK starts social distancing after new model points to 260 000 potential deaths. BMJ. 2020 Mar 17;368:m1089. doi: 10.1136/bmj.m1089. No abstract available.

  PMID: 32184205 BACKGROUND

• Duan L, Zhu G. Psychological interventions for people affected by the COVID-19 epidemic. Lancet Psychiatry. 2020 Apr;7(4):300-302. doi: 10.1016/S2215-0366(20)30073-0. Epub 2020 Feb 19. No abstract available.

  PMID: 32085840 BACKGROUND

• Baud D, Qi X, Nielsen-Saines K, Musso D, Pomar L, Favre G. Real estimates of mortality following COVID-19 infection. Lancet Infect Dis. 2020 Jul;20(7):773. doi: 10.1016/S1473-3099(20)30195-X. Epub 2020 Mar 12. No abstract available.

  PMID: 32171390 BACKGROUND

• Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24.

  PMID: 31986264 BACKGROUND

• 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.

  PMID: 32171076 BACKGROUND

• Chan JF, Yuan S, Kok KH, To KK, Chu H, Yang J, Xing F, Liu J, Yip CC, Poon RW, Tsoi HW, Lo SK, Chan KH, Poon VK, Chan WM, Ip JD, Cai JP, Cheng VC, Chen H, Hui CK, Yuen KY. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet. 2020 Feb 15;395(10223):514-523. doi: 10.1016/S0140-6736(20)30154-9. Epub 2020 Jan 24.

  PMID: 31986261 BACKGROUND

• Ebrahim SH, Memish ZA. COVID-19: preparing for superspreader potential among Umrah pilgrims to Saudi Arabia. Lancet. 2020 Mar 14;395(10227):e48. doi: 10.1016/S0140-6736(20)30466-9. Epub 2020 Feb 27. No abstract available.

  PMID: 32113506 BACKGROUND

• Baden LR, Rubin EJ. Covid-19 - The Search for Effective Therapy. N Engl J Med. 2020 May 7;382(19):1851-1852. doi: 10.1056/NEJMe2005477. Epub 2020 Mar 18. No abstract available.

  PMID: 32187463 BACKGROUND

• Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, Ruan L, Song B, Cai Y, Wei M, Li X, Xia J, Chen N, Xiang J, Yu T, Bai T, Xie X, Zhang L, Li C, Yuan Y, Chen H, Li H, Huang H, Tu S, Gong F, Liu Y, Wei Y, Dong C, Zhou F, Gu X, Xu J, Liu Z, Zhang Y, Li H, Shang L, Wang K, Li K, Zhou X, Dong X, Qu Z, Lu S, Hu X, Ruan S, Luo S, Wu J, Peng L, Cheng F, Pan L, Zou J, Jia C, Wang J, Liu X, Wang S, Wu X, Ge Q, He J, Zhan H, Qiu F, Guo L, Huang C, Jaki T, Hayden FG, Horby PW, Zhang D, Wang C. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020 May 7;382(19):1787-1799. doi: 10.1056/NEJMoa2001282. Epub 2020 Mar 18.

  PMID: 32187464 BACKGROUND

• 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. No abstract available.

  PMID: 32043983 BACKGROUND

• Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, Ren R, Leung KSM, Lau EHY, Wong JY, Xing X, Xiang N, Wu Y, Li C, Chen Q, Li D, Liu T, Zhao J, Liu M, Tu W, Chen C, Jin L, Yang R, Wang Q, Zhou S, Wang R, Liu H, Luo Y, Liu Y, Shao G, Li H, Tao Z, Yang Y, Deng Z, Liu B, Ma Z, Zhang Y, Shi G, Lam TTY, Wu JT, Gao GF, Cowling BJ, Yang B, Leung GM, Feng Z. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. N Engl J Med. 2020 Mar 26;382(13):1199-1207. doi: 10.1056/NEJMoa2001316. Epub 2020 Jan 29.

  PMID: 31995857 BACKGROUND

• Hellewell J, Abbott S, Gimma A, Bosse NI, Jarvis CI, Russell TW, Munday JD, Kucharski AJ, Edmunds WJ; Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group; Funk S, Eggo RM. Feasibility of controlling COVID-19 outbreaks by isolation of cases and contacts. Lancet Glob Health. 2020 Apr;8(4):e488-e496. doi: 10.1016/S2214-109X(20)30074-7. Epub 2020 Feb 28.

  PMID: 32119825 BACKGROUND

• Vincent MJ, Bergeron E, Benjannet S, Erickson BR, Rollin PE, Ksiazek TG, Seidah NG, Nichol ST. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J. 2005 Aug 22;2:69. doi: 10.1186/1743-422X-2-69.

  PMID: 16115318 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.

  PMID: 32205204 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.

  PMID: 32020029 BACKGROUND

• Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends. 2020 Mar 16;14(1):72-73. doi: 10.5582/bst.2020.01047. Epub 2020 Feb 19.

  PMID: 32074550 BACKGROUND

• Bacharier LB, Guilbert TW, Mauger DT, Boehmer S, Beigelman A, Fitzpatrick AM, Jackson DJ, Baxi SN, Benson M, Burnham CD, Cabana M, Castro M, Chmiel JF, Covar R, Daines M, Gaffin JM, Gentile DA, Holguin F, Israel E, Kelly HW, Lazarus SC, Lemanske RF Jr, Ly N, Meade K, Morgan W, Moy J, Olin T, Peters SP, Phipatanakul W, Pongracic JA, Raissy HH, Ross K, Sheehan WJ, Sorkness C, Szefler SJ, Teague WG, Thyne S, Martinez FD. Early Administration of Azithromycin and Prevention of Severe Lower Respiratory Tract Illnesses in Preschool Children With a History of Such Illnesses: A Randomized Clinical Trial. JAMA. 2015 Nov 17;314(19):2034-2044. doi: 10.1001/jama.2015.13896.

  PMID: 26575060 BACKGROUND

• Hulswit RJ, de Haan CA, Bosch BJ. Coronavirus Spike Protein and Tropism Changes. Adv Virus Res. 2016;96:29-57. doi: 10.1016/bs.aivir.2016.08.004. Epub 2016 Sep 13.

  PMID: 27712627 BACKGROUND

• Arabi YM, Deeb AM, Al-Hameed F, Mandourah Y, Almekhlafi GA, Sindi AA, Al-Omari A, Shalhoub S, Mady A, Alraddadi B, Almotairi A, Al Khatib K, Abdulmomen A, Qushmaq I, Solaiman O, Al-Aithan AM, Al-Raddadi R, Ragab A, Al Harthy A, Kharaba A, Jose J, Dabbagh T, Fowler RA, Balkhy HH, Merson L, Hayden FG; Saudi Critical Care Trials group. Macrolides in critically ill patients with Middle East Respiratory Syndrome. Int J Infect Dis. 2019 Apr;81:184-190. doi: 10.1016/j.ijid.2019.01.041. Epub 2019 Jan 25.

  PMID: 30690213 BACKGROUND

• Retallack H, Di Lullo E, Arias C, Knopp KA, Laurie MT, Sandoval-Espinosa C, Mancia Leon WR, Krencik R, Ullian EM, Spatazza J, Pollen AA, Mandel-Brehm C, Nowakowski TJ, Kriegstein AR, DeRisi JL. Zika virus cell tropism in the developing human brain and inhibition by azithromycin. Proc Natl Acad Sci U S A. 2016 Dec 13;113(50):14408-14413. doi: 10.1073/pnas.1618029113. Epub 2016 Nov 29.

  PMID: 27911847 BACKGROUND

• To KK, Tsang OT, Leung WS, Tam AR, Wu TC, Lung DC, Yip CC, Cai JP, Chan JM, Chik TS, Lau DP, Choi CY, Chen LL, Chan WM, Chan KH, Ip JD, Ng AC, Poon RW, Luo CT, Cheng VC, Chan JF, Hung IF, Chen Z, Chen H, Yuen KY. Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study. Lancet Infect Dis. 2020 May;20(5):565-574. doi: 10.1016/S1473-3099(20)30196-1. Epub 2020 Mar 23.

  PMID: 32213337 BACKGROUND

• Zou L, Ruan F, Huang M, Liang L, Huang H, Hong Z, Yu J, Kang M, Song Y, Xia J, Guo Q, Song T, He J, Yen HL, Peiris M, Wu J. SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients. N Engl J Med. 2020 Mar 19;382(12):1177-1179. doi: 10.1056/NEJMc2001737. Epub 2020 Feb 19. No abstract available.

  PMID: 32074444 BACKGROUND

• Tisdale JE, Jaynes HA, Kingery JR, Mourad NA, Trujillo TN, Overholser BR, Kovacs RJ. Development and validation of a risk score to predict QT interval prolongation in hospitalized patients. Circ Cardiovasc Qual Outcomes. 2013 Jul;6(4):479-87. doi: 10.1161/CIRCOUTCOMES.113.000152. Epub 2013 May 28.

  PMID: 23716032 BACKGROUND

• Omrani AS, Pathan SA, Thomas SA, Harris TRE, Coyle PV, Thomas CE, Qureshi I, Bhutta ZA, Mawlawi NA, Kahlout RA, Elmalik A, Azad AM, Daghfal J, Mustafa M, Jeremijenko A, Soub HA, Khattab MA, Maslamani MA, Thomas SH. Randomized double-blinded placebo-controlled trial of hydroxychloroquine with or without azithromycin for virologic cure of non-severe Covid-19. EClinicalMedicine. 2020 Dec;29:100645. doi: 10.1016/j.eclinm.2020.100645. Epub 2020 Nov 20.

  PMID: 33251500 DERIVED

MeSH Terms

Conditions

COVID-19; Coronavirus Infections; Respiration Disorders; Emergencies

Interventions

Hydroxychloroquine; Azithromycin

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Study Officials

• Tim R Harris

  Hamad Medical Corporation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blinded trial
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Tim Richard Edmund Harris

Study Record Dates

• First Submitted: April 12, 2020
• First Posted: April 16, 2020
• Study Start: April 14, 2020
• Primary Completion: August 14, 2020
• Study Completion: August 30, 2020
• Last Updated: February 23, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

QA (1)