Ivermectin vs Combined Hydroxychloroquine and Antiretroviral Drugs (ART) Among Asymptomatic COVID-19 Infection (IDRA-COVID19)

• ClinicalTrials.gov Identifier: NCT04435587
• Recruitment Status: Unknown
• First Posted: June 17, 2020
• Last Update Posted: January 11, 2021
• Sponsor: Mahidol University
• Information provided by (Responsible Party): Yupin Suputtamongkol, Mahidol University

Study Description

Brief Summary:

This is an open label randomised controlled study of oral ivermectin (600 mcg/kg/d* 3 day) versus combined of hydroxychloroquine plus darunavir/ ritonavir for 5 days treatment among asymptomatic carrier of SAR-CoV2 adult Thai population. Both study treatment regimens will have oral zinc sulfate combination treatment ( 200mg. twice daily). Outcomes include safety and duration of detectable of SAR-CoV2 in nasopharyngeal/ throat (NP) swab by polymerase chain reaction amplification (PCR) after treatment. 40-50 patients in each treatment arm is planned, with an interim analysis when approximately 50% of cases is enrolled.

Condition or disease	Intervention/treatment	Phase
Asymptomatic Infections; SARS-CoV2 Infection	Drug: Ivermectin Pill; Drug: Combined ART/hydroxychloroquine	Phase 4

Detailed Description:

• Study procedure will be carried out after informed consent is obtained.
• Baseline physical exam and laboratory investigations will be performed.
• Eligible patients will be randomized to one of the two treatment arms.
• Symptoms and signs will be monitored daily.
• NP swab will be done at day5-7, and prior to discharge.
• Complete blood counts, blood chemistries, electrocardiography will be performed for adverse event monitoring within 5 days after end of study drugs' administration.
• Patients will be discharged at 2- 4 weeks after hospitalization, according to PCR results.
• There will be 1-2 follow up visit at out patient clinic for NP swab (patients with +ve last NP swab before discharge), and blood tests.
• Additional 5-8 ml. of EDTA blood will be taken at baseline and weekly for antibody detection.
• Interim analysis of both safety and efficacy will be performed when approximately 50% of enrollment is achieved.
• Intention to treat analysis is planned at the completion of enrollment.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Masking Description: PCR for SAR-CoV2 detection will be performed by technician without knowledge of treatment arm
• Primary Purpose: Treatment
• Official Title: Comparative Efficacy of Ivermectin Versus Combination of Hydroxychloroquine Plus Darunavir/ Ritonavir for Shortening Duration of SARS-CoV2 Detection From Respiratory Secretion Among Asymptomatic or Afebrile COVID-19 Infection
• Actual Study Start Date: July 13, 2020
• Estimated Primary Completion Date: June 2021
• Estimated Study Completion Date: November 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: ivermectin; Combination of; oral ivermectin 600 mcg/kg/day once daily for 3 days; Zinc sulfate (100mg/tab) 2 tab every 12 hours for 3 days	Drug: Ivermectin Pill; 3 days of once daily oral ivermectin 600mcg/kg/d; Other Name: Vermectin
Active Comparator: ART/hydroxychloroquine; Combination of; Day1 hydroxychloroquine 400mg bid, then 200mg bid on Day 2-5; Darunavir/ritonavir (400/100mg) every 12 hours for 5 days; Zinc sulfate (100/tab) 2 tab every 12 hours for 5 days	Drug: Combined ART/hydroxychloroquine; Day 1 hydroxychloroquine 400mg bid, Day2-5 hydroxychloroquine 200mg bid; Darunavir/ritonavir (400/100mg) q 12 hours for 5 days; Other Name: combined darunavir/ritonavir/hydroxychloroquine

Outcome Measures

Primary Outcome Measures :

1. Adverse event rates [ Time Frame: after first dose until day 28 of follow up ]
   Comparison of adverse event rates between treatment arms
2. Efficacy for shortening duration of SAR-CoV2 detection by PCR [ Time Frame: weekly after treatment until 4th week ]
   comparison of median duration for detectable SAR-CoV2 by PCR from NP swab in each arm

Secondary Outcome Measures :

1. Antibody detection rates [ Time Frame: weekly after treatment until 4th week ]
   comparison of median duration for total antibody detection in each arm

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• SAR-CoV2 detected by PCR from NP swab
• Asymptomatic or upper respiratory symptoms such as runny noses
• No history of fever or oral Temp <37.8 degree celsius
• informed consent obtained

Exclusion Criteria:

• Fever or respiratory rate >24/minute or oxygen saturation at room air< 94%
• Any serious co-morbidity such as chronic lung disease, chronic kidney disease, cardiovascular diseases, arrythmia, diabetes mellitus with HbA1C > 8%, chronic liver disease, lymphocyte count <1,000cell/cu.mm.
• History of ivermectin or any of the study drug allergy.
• Concomitant medication with potential drug interaction with any of the study drugs such as alfuzosin, colchicine, ergot derivatives, cisapride, simvastatin and rifampicin
• Pregnant or lactating woman

Contacts and Locations

Contacts

Contact: Yupin Suputtamongkol, MD; +66817545573; ysuputtamongkol@gmail.com

Contact: Rujipas Sirijatuphat, MD; +66840665961

Locations

Thailand

Siriraj Hospital; Recruiting

Bangkok Noi, Bangkok, Thailand, 10700

Contact: Yupin Suputtamongkol, MD +66817545573 ysuputtamongkol@gmail.com

Contact: Rujipas Sirijatuphat, MD +66840665961 rujipas21@gmail.com

Sub-Investigator: Susan Assanasen, MD

Sub-Investigator: Nasikarn Angkasekwinai, MD

Sub-Investigator: Methee Chayakulkeeree, MD

Sub-Investigator: Ranistha Ratanarat, MD

Sub-Investigator: Krittika Teerapuncharoen, MD

Sub-Investigator: Dechathorn Rasameekultana, MD

Sub-Investigator: Sireethorn Nimitvilai, MD

Siriaj Hospital; Recruiting

Bangkok, N/A = Not Applicable, Thailand, 10700

Contact: Yupin Suputtamongkol, MD 66817545573 ysuputtamongkol@gmail.com

Contact: Rujipas Sirijatuphat rujipas.sir@mahidol.ac.th

Principal Investigator: Dechathorn Rassamekulthana, MD

Sireethorn Nimitvilai; Recruiting

Amphoe Maueng, Nakhonpathom, Thailand, 73000

Contact: Sireethorn Nimitvilai, MD sireethorn200@gmail.com

Golden Jubilee Medical Center; Recruiting

Phutthamonthon District, Nakhonpathom, Thailand, 73170

Contact: Dechathorn Rassamekulthana, MD dechathorn.ras@mahidol.ac.th

Contact: Nuttawut Rongkiettechakorn, MD nuttawut.sir@mahidol.edu

Sponsors and Collaborators

Mahidol University

Investigators

• Principal Investigator: Yupin Suputtamongkol, MD; Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University

More Information

• Responsible Party: Yupin Suputtamongkol, Professor, Mahidol University
• ClinicalTrials.gov Identifier: NCT04435587
• Other Study ID Numbers: 323/2563 (IRB3)
• First Posted: June 17, 2020
• Last Update Posted: January 11, 2021
• Last Verified: January 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Yupin Suputtamongkol, Mahidol University:

ivermectin; hydroxychloroquine/darunavir/ritonavir; SAR-CoV2; asymptomatic infection; zinc sulfate

Additional relevant MeSH terms:

COVID-19; Coronavirus Infections; Coronaviridae Infections; Hydroxychloroquine; Infections; Communicable Diseases; Asymptomatic Infections; Disease Attributes; Pathologic Processes; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Virus Diseases; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Asymptomatic Diseases; Ritonavir; Darunavir; Ivermectin; HIV Protease Inhibitors; Viral Protease Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-HIV Agents; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents