Hydroxychloroquine and Nitazoxanide Combination Therapy for COVID-19

NCT04361318 | Unknown Phase 2 DMC

• 1 other identifier: HCQ/NTZ
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief Summary

In December 2019, a new infectious respiratory disease emerged in Wuhan, Hubei province, China. An initial cluster of infections was linked to Huanan seafood market, potentially due to animal contact. Subsequently, human-to-human transmission occurred and the disease, now termed coronavirus disease 19 (COVID-19) rapidly spread within China and all over the world. A novel coronavirus, SARS-coronavirus 2 (SARS-CoV-2), which is closely related to SARS-CoV, was detected in patients and is believed to be the etiologic agent of the new lung disease. The causative agent of the current COVID-19 pandemic, SARS-CoV-2, is a single stranded positive sense RNA virus that is closely related to severe acute respiratory syndrome coronavirus (SARS-CoV).

Conditions

COVID-19

Keywords

Hydroxychloroquine; Nitazoxanide; COVID-19

Outcome Measures

Primary Outcomes (1)

• Number of patients with COVID-19-negative PCR

  PCR analysis of COVID-19 RNA in patients

  within 10 days to become PCR negative

Secondary Outcomes (9)

• Number of patients with improved respiratory rate

  within 30 days

• Number of patients with improved PaO2

  within 30 days

• Number of patients with normalized Serum IL6

  within 30 days

• Number of patients with normalized Serum TNFα

  within 30 days

• Number of patients with normalized Serum iron

  within 30 days

Study Arms (2)

Hydroxychloroquine plus Nitazoxanide

EXPERIMENTAL

200 mg of Hydroxychloroquine orally three times daily for 10 days plus 500 mg of Nitazoxanide orally twice daily for 6 days

Combination Product: Hydroxychloroquine plus Nitazoxanide

Standard care

ACTIVE COMPARATOR

Standard care delivered in the COVID-19 isolation hospitals.

Other: Standard care

Interventions

Hydroxychloroquine plus Nitazoxanide COMBINATION_PRODUCT

Both hydroxychloroquine \& nitazoxanide will be administered orally to participating patients

Also known as: drug therapy

Hydroxychloroquine plus Nitazoxanide

Standard care OTHER

Oxygen administered via ventilator. In addition, antipyretic "paracetamol" may be added if necessary

Standard care

Eligibility Criteria

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

You may qualify if:

• Confirmed cases of COVID-19 (Positive RT-PCR)
• Newly diagnosed symptomatic patients.
• Adults (18-65 Years old)
• Both sexes

You may not qualify if:

• Patients with abnormal liver function (ALT, AST), chronic kidney disease or dialysis (CrCl\< 30 ml/min)
• Pregnant women or women who are breastfeeding
• Immunocompromised patients taking medication upon screening
• Subjects with comorbid condition like hypertension, cardiovascular disease, diabetes mellites, asthma, COPD, malignancy
• Patients having allergy to Hydroxychloroquine and/or Nitazoxanide
• Patients with contraindication towards the study medication including retinopathy, G6PD deficiency and QT prolongation.

Sponsors & Collaborators

• Tanta University: lead

Related Publications (15)

• 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

• Wang C, Horby PW, Hayden FG, Gao GF. A novel coronavirus outbreak of global health concern. Lancet. 2020 Feb 15;395(10223):470-473. doi: 10.1016/S0140-6736(20)30185-9. Epub 2020 Jan 24. No abstract available.

  PMID: 31986257 BACKGROUND

• Yu P, Zhu J, Zhang Z, Han Y. A Familial Cluster of Infection Associated With the 2019 Novel Coronavirus Indicating Possible Person-to-Person Transmission During the Incubation Period. J Infect Dis. 2020 May 11;221(11):1757-1761. doi: 10.1093/infdis/jiaa077.

  PMID: 32067043 BACKGROUND

• Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res. 2020 Jun;178:104787. doi: 10.1016/j.antiviral.2020.104787. Epub 2020 Apr 3.

  PMID: 32251768 BACKGROUND

• Biot C, Daher W, Chavain N, Fandeur T, Khalife J, Dive D, De Clercq E. Design and synthesis of hydroxyferroquine derivatives with antimalarial and antiviral activities. J Med Chem. 2006 May 4;49(9):2845-9. doi: 10.1021/jm0601856.

  PMID: 16640347 BACKGROUND

• Marmor MF, Kellner U, Lai TY, Melles RB, Mieler WF; American Academy of Ophthalmology. Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision). Ophthalmology. 2016 Jun;123(6):1386-94. doi: 10.1016/j.ophtha.2016.01.058. Epub 2016 Mar 16.

  PMID: 26992838 BACKGROUND

• Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, Liu X, Zhao L, Dong E, Song C, Zhan S, Lu R, Li H, Tan W, Liu D. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020 Jul 28;71(15):732-739. doi: 10.1093/cid/ciaa237.

  PMID: 32150618 BACKGROUND

• Raoult D, Houpikian P, Tissot Dupont H, Riss JM, Arditi-Djiane J, Brouqui P. Treatment of Q fever endocarditis: comparison of 2 regimens containing doxycycline and ofloxacin or hydroxychloroquine. Arch Intern Med. 1999 Jan 25;159(2):167-73. doi: 10.1001/archinte.159.2.167.

  PMID: 9927100 BACKGROUND

• Liu J, Cao R, Xu M, Wang X, Zhang H, Hu H, Li Y, Hu Z, Zhong W, Wang M. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov. 2020 Mar 18;6:16. doi: 10.1038/s41421-020-0156-0. eCollection 2020. No abstract available.

  PMID: 32194981 BACKGROUND

• Colson P, Rolain JM, Lagier JC, Brouqui P, Raoult D. Chloroquine and hydroxychloroquine as available weapons to fight COVID-19. Int J Antimicrob Agents. 2020 Apr;55(4):105932. doi: 10.1016/j.ijantimicag.2020.105932. Epub 2020 Mar 4. No abstract available.

  PMID: 32145363 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

• Rossignol JF. Nitazoxanide: a first-in-class broad-spectrum antiviral agent. Antiviral Res. 2014 Oct;110:94-103. doi: 10.1016/j.antiviral.2014.07.014. Epub 2014 Aug 7.

  PMID: 25108173 BACKGROUND

• Hong SK, Kim HJ, Song CS, Choi IS, Lee JB, Park SY. Nitazoxanide suppresses IL-6 production in LPS-stimulated mouse macrophages and TG-injected mice. Int Immunopharmacol. 2012 May;13(1):23-7. doi: 10.1016/j.intimp.2012.03.002. Epub 2012 Mar 17.

  PMID: 22430099 BACKGROUND

• 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. No abstract available.

  PMID: 32113510 BACKGROUND

• Lu H, Stratton CW, Tang YW. Outbreak of pneumonia of unknown etiology in Wuhan, China: The mystery and the miracle. J Med Virol. 2020 Apr;92(4):401-402. doi: 10.1002/jmv.25678. Epub 2020 Feb 12. No abstract available.

  PMID: 31950516 BACKGROUND

MeSH Terms

Conditions

COVID-19

Interventions

Hydroxychloroquine; nitazoxanide; Drug Therapy; Standard of Care

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Therapeutics; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Kamal Okasha, MD, PhD

  Tanta University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kamal Okasha, MD, PhD

CONTACT

+201004706770; vp_research@unv.tanta.edu.eg

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: a double blind randomized controlled parallel study
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice-President of Postgraduate Studies and Research Affairs

Study Record Dates

• First Submitted: April 18, 2020
• First Posted: April 24, 2020
• Study Start: May 1, 2020
• Primary Completion: October 1, 2020
• Study Completion: December 1, 2020
• Last Updated: April 24, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share