Efficacy and Tolerability of Hydroxychloroquine in Adult Patients With COVID-19

NCT04384380 | Completed DMC

• 1 other identifier: TYGH109014
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

The effective medical treatment against COVID-19 infection is still unknown. Chloroquine phosphate is a well-known antimalarial drug which has been on the market for many years. Recently, in vitro study shown that Chloroquine is effective at both entry and at post-entry stages of the COVID-19 infection of Vero E6 cells with promising results. Chloroquine is also an immune-modifier and could distribute to the whole body including lung. Also, chloroquine is cheap and safe, and could be a promising agent against COVID-19 infection. However, only hydroxychloroquine (HCQ) with the extra hydroxyl group is available in Taiwan. Therefore, hydroxychloroquine instead become the best choice for the treatment candidate, since it shows higher in vitro potency (EC50) against COVID-19 with lower toxicity while retaining the original effect which compared with chloroquine.

Conditions

Coronavirus Infection

Keywords

COVID-19

Outcome Measures

Primary Outcomes (1)

• Time to negatively RT-PCR

  To evaluate the efficacy of HCQ, with respect to the time to negatively RT-PCR assessments in COVID-19 patients.

  14 days

Secondary Outcomes (2)

• Virologic assessment

  14 days

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  28 days

Study Arms (2)

HCQ in adult Patients with COVID-19

EXPERIMENTAL

The administration plan of HCQ is 400 mg bid on Day 1 and 200 mg bid for 6 days on Day 2-7.

Drug: Hydroxychloroquine Sulfate 200 MG [Plaquenil]

standard of care treatment (SOC)

NO INTERVENTION

The comparison group will receive standard of care, i.e., supportive treatment for subjects with mild COVID-19 clinical illness.

Interventions

Hydroxychloroquine Sulfate 200 MG [Plaquenil] DRUG

Hydroxychloroquine Sulfate is 400 mg bid on Day 1 and 200 mg bid for 6 days on Day 2-7.

Also known as: Plaquenil

HCQ in adult Patients with COVID-19

Eligibility Criteria

• Age: 20 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who had fever (central temperature ≥38°C) or acute upper respiratory symptoms and laboratory confirmation (rRT-PCR) for COVID-19, with available same type of upper respiratory tract specimens from screening evaluation to the initial testing within 4 days of initial testing
• Patients have mild (no pneumonia) to moderate disease (pneumonia without respiratory distress) according to the following World Health Organization (WHO) definition of COVID-19 clinical syndromes:
• Mild (Mild illness):
• Patients with uncomplicated upper respiratory tract viral infection, may have non-specific symptoms such as fever, fatigue, cough (with or without sputum production), anorexia, malaise, muscle pain, sore throat, dyspnea, nasal congestion, or headache. Rarely, patients may also present with diarrhoea, nausea and vomiting.
• Moderate (Pneumonia):
• Adult with pneumonia but no signs of severe pneumonia and no need for supplemental oxygen.
• Willing and able to comply with the study procedure and sign a written informed consent

You may not qualify if:

• Patients with the medical history of hypersensitivity to chloroquine, chloroquinine, or hydroxychloroquine
• Patients with retinal disease, hearing loss, severe neurological and mental illness
• Patients with pancreatitis
• Patients with severe lung, liver (alanine aminotransferase (ALT)/aspartate aminotransferase (AST) elevation more than 3 times the normal upper limit), kidney (estimated glomerular filtration rate \[eGFR\] \<30 mL/min/1.73m2, using the MDRD or CKD-EPI methods), brain, haematological diseases or other important systemic diseases
• Medical history of uncontrolled but clinically significant abnormal cardiac conduction abnormalities at electrocardiogram (ECG) at screening, any history or evidence of long QT syndrome or QTcF interval \>450 msec for males and \>470 msec for females (according to Fridericia's correction) at screening
• Known HIV infection; active hepatitis B or C without concurrent treatment (positive tests for hepatitis B \[both HBsAg and HBeAg\], or high titer of hepatitis C ribonucleic acid \[RNA\] \>800,000 IU/ml)
• Uncontrolled and unstable concurrent medical condition including psychiatric disorders and alcohol/substance dependence/abuse that will jeopardize the safety of the patient, interfere with the objectives of the study, or affect the patient compliance with study requirements, as determined by the Investigator
• Patients with concomitant use of medications that alter the absorption or excretion of hydroxychloroquine
• Patients were considered to be unable to complete the study, or not suitable for the study judged by Investigators
• Pregnant or breast-feeding women

Sponsors & Collaborators

• Taoyuan General Hospital: lead
• Center for Drug Evaluation, Taiwan: collaborator
• Centers for Disease Control, Taiwan: collaborator
• Taiwan Food and Drug Administration: collaborator
• National Health Research Institutes, Taiwan: collaborator

Study Sites (1)

Taoyuan General Hospital, Ministry of Health and Welfare

Taoyuan, 320, Taiwan

Location

Related Publications (5)

• Cheng SC, Chang YC, Fan Chiang YL, Chien YC, Cheng M, Yang CH, Huang CH, Hsu YN. First case of Coronavirus Disease 2019 (COVID-19) pneumonia in Taiwan. J Formos Med Assoc. 2020 Mar;119(3):747-751. doi: 10.1016/j.jfma.2020.02.007. Epub 2020 Feb 26.

  PMID: 32113824 RESULT

• 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 RESULT

• Zhang W, Du RH, Li B, Zheng XS, Yang XL, Hu B, Wang YY, Xiao GF, Yan B, Shi ZL, Zhou P. Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes. Emerg Microbes Infect. 2020 Feb 17;9(1):386-389. doi: 10.1080/22221751.2020.1729071. eCollection 2020.

  PMID: 32065057 RESULT

• 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.

  PMID: 32173110 RESULT

• 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 RESULT

MeSH Terms

Conditions

Coronavirus Infections; COVID-19

Interventions

Hydroxychloroquine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Shu-Hsing Cheng, Dr.

  Taoyuan General Hospital, Ministry of Health and Welfare

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: The study will employ an open-label parallel design, to evaluate the efficacy and safety between hydroxychloroquine sulfate (plaquenil) and controlled standard of care treatment. The administration plan of HCQ is 400 mg bid on Day 1 and 200 mg bid for 6 days on Day 2-7. All of the enrolled subjects will receive standard of care. The comparison group will receive standard of care, i.e., supportive treatment for subjects with mild COVID-19 clinical illness.

Study Record Dates

• First Submitted: April 7, 2020
• First Posted: May 12, 2020
• Study Start: April 1, 2020
• Primary Completion: May 31, 2020
• Study Completion: May 31, 2020
• Last Updated: August 4, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)