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

Primary Purpose

Coronavirus Infection

Status

Completed

Phase

Not Applicable

Locations

Taiwan

Study Type

Interventional

Intervention

Hydroxychloroquine Sulfate 200 MG [Plaquenil]

About this trial

This is an interventional treatment trial for Coronavirus Infection focused on measuring COVID-19

Eligibility Criteria

20 Years - 79 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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

Sites / Locations

Taoyuan General Hospital, Ministry of Health and Welfare

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

HCQ in adult Patients with COVID-19

standard of care treatment (SOC)

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Virologic assessment

To evaluate the efficacy of HCQ in the aspect of virologic assessments in COVID-19 patients

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

To evaluate the safety and tolerability of HCQ

Full Information

NCT ID

NCT04384380

First Posted

April 7, 2020

Last Updated

July 31, 2020

Sponsor

Taoyuan General Hospital

Collaborators

Center for Drug Evaluation, Taiwan, Centers for Disease Control, Taiwan, Taiwan Food and Drug Administration, National Health Research Institutes, Taiwan

1. Study Identification

Unique Protocol Identification Number

NCT04384380

Brief Title

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

Official Title

A Multi-center, Randomized, Open-label, Controlled Trial to Evaluate the Efficacy and Tolerability of Hydroxychloroquine (HCQ) in Adult Patients With Mild to Moderate Coronavirus Disease (COVID-19) Compared to Standard of Care Treatment

Study Type

Interventional

2. Study Status

Record Verification Date

March 2020

Overall Recruitment Status

Completed

Study Start Date

April 1, 2020 (Actual)

Primary Completion Date

May 31, 2020 (Actual)

Study Completion Date

May 31, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Taoyuan General Hospital

Collaborators

Center for Drug Evaluation, Taiwan, Centers for Disease Control, Taiwan, Taiwan Food and Drug Administration, National Health Research Institutes, Taiwan

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

Detailed Description

On December 31, 2019, an outbreak of respiratory illness later proved to be caused by a novel coronavirus, officially named Coronavirus Disease 2019 (COVID-19), was notified first in Wuhan, a city of Hubei province, People's Republic of China (PRC). COVID-19 rapidly spreads in China and to other parts of the world. Currently more than 370,000 laboratory-confirmed cases have been reported worldwide, and the case count has been rising daily, and caused a global health emergency. As of March 29, 2020, there were 298 confirmed cases in Taiwan. This is a multi-center, randomized, open-label, controlled trial to evaluate the efficacy and tolerability of Hydroxychloroquine Sulfate (HCQ) in adult Patients with mild to moderate coronavirus disease (COVID-19) compared to standard of care treatment (SOC). The primary endpoint for the study is to evaluate the efficacy of HCQ, with respect to the time to negatively rRT-PCR assessments from the randomization date up to 14 days. The secondary endpoint is to evaluate the efficacy of HCQ in the aspect of virological assessments and the change of clinical symptoms. In addition, the safety and tolerability of HCQ will be evaluated during treatment period in COVID-19 patients.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Coronavirus Infection

Keywords

COVID-19

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Model Description

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.

Masking

None (Open Label)

Allocation

Randomized

Enrollment

33 (Actual)

8. Arms, Groups, and Interventions

Arm Title

HCQ in adult Patients with COVID-19

Arm Type

Experimental

Arm Description

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

Arm Title

standard of care treatment (SOC)

Arm Type

No Intervention

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Hydroxychloroquine Sulfate 200 MG [Plaquenil]

Other Intervention Name(s)

Plaquenil

Intervention Description

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

Primary Outcome Measure Information:

Title

Time to negatively RT-PCR

Description

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

Time Frame

14 days

Secondary Outcome Measure Information:

Title

Virologic assessment

Description

To evaluate the efficacy of HCQ in the aspect of virologic assessments in COVID-19 patients

Time Frame

14 days

Title

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

Description

To evaluate the safety and tolerability of HCQ

Time Frame

28 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

79 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Shu-Hsing Cheng, Dr.

Organizational Affiliation

Taoyuan General Hospital, Ministry of Health and Welfare

Official's Role

Principal Investigator

Facility Information:

Facility Name

Taoyuan General Hospital, Ministry of Health and Welfare

City

Taoyuan City

ZIP/Postal Code

320

Country

Taiwan

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

The study outcome will be shared with the experts and persons interested in this field.

Citations:

PubMed Identifier

32113824

Citation

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.

Results Reference

result

PubMed Identifier

31986264

Citation

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. Erratum In: Lancet. 2020 Jan 30;:

Results Reference

result

PubMed Identifier

32065057

Citation

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.

Results Reference

result

PubMed Identifier

32173110

Citation

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.

Results Reference

result

PubMed Identifier

32205204

Citation

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. 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.

Results Reference

result

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

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