Study to Investigate the Clinical Efficacy of Isoquercetin in Patients With COVID-19

A Randomized, Open-labelled and Controlled Clinical Trial to Investigate the Clinical Efficacy of Isoquercetin in the Treatment of Mild-to-moderate Hospitalised COVID-19 Patients

The purpose of this study is to investigate the clinical efficacy of Isoquercetin in preventing disease progression and symptoms improvement in mild-to-moderate hospitalised COVID-19 patients.

Study Overview

• Status: Unknown
• Conditions: Covid19
• Intervention / Treatment: Drug: Hospital standard of care for COVID-19; Drug: Isoquercetin

Detailed Description

This is an open-labelled, randomized and multi-centre clinical trial in subjects with RT-PCR confirmed SARS-CoV-2 infection with mild-to-moderate symptoms, and who are currently admitted to the hospital for diagnosis of COVID-19. The study has two arms: hospital standard COVID-19 care (Control group) and hospital standard COVID-19 care + Isoquercetin (Isoquercetin group). The recruited subjects will be placed into either group by an electronic randomization process. Patients in the Isoquercetin group will receive a daily dose of 1000 mg Isoquercetin as 4 x 250 mg Isoquercetin capsules as add-on therapy in addition to the hospital standard COVID-19 care. The Isoquercetin treatment will continue for 28 days.

• Study Type: Interventional
• Enrollment (Anticipated): 250
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Dr. Suman Pant, MD/MBBS; Phone Number: 0977-14254220; Email: suman.p@fph.tu.ac.th
• Study Contact Backup: Name: Dr. Bikal Shrestha, MD/MBBS; Phone Number: 0977-984-1262421; Email: bikalshrestha@naihs.edu.np

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Adults aged 18 years and above.
2. Confirmed SARS-CoV-2 infection by PCR/RT-PCR. Patients with positive point of care tests can be randomised but have to be confirmed for SARS-CoV-2 by RT-PCR.
3. Presence of symptoms consistent with COVID-19 (e.g. shortness of breath, cough, sputum, muscle aches, headache, fatigue, sore throat, loss or change to sense of smell and/or taste, rhinorrhoea and anorexia).
4. WHO 10-point Clinical Progression Scale score of 4 to 5
5. Patient requires hospitalisation due to severity of COVID-19 or comorbidities if score 3 on the WHO 10-point Clinical Progression Scale.
6. Frailty score of ≤6.
7. Patient able to provide informed consent.
8. Females of child-bearing potential must be non-lactating, must have a negative pregnancy test at Screening, and must agree to continue using contraception throughout the study and for 4 weeks after study completion.

Exclusion Criteria:

1. Severe or critical COVID-19, e.g.:

   • Respiratory rate ≥ 30 breaths per minute OR
   • Heart rate ≥ 125 beats per minute OR
   • Respiratory failure, defined as clinical need for high-flow oxygen therapy, non- invasive positive pressure ventilation or endotracheal intubation and mechanical ventilation OR
   • Shock, defined as systolic blood pressure <90 mm Hg or diastolic blood pressure <60 mm Hg or requiring vasopressors OR
   • Multi-organ dysfunction/failure (WHO Clinical Progression Scale score ≥6)
2. Hospitalisation for reasons other than severity of COVID-19 or comorbidities (e.g. social reasons, local policies, isolation/quarantine).
3. Active bleeding or high risk for bleeding (e.g. known acute gastrointestinal ulcer).
4. History of significant haemorrhage (requiring hospitalisation or transfusion) outside of a surgical setting within the last 24 months.
5. Familial bleeding diathesis.
6. Glucose-6-phosphate dehydrogenase deficiency.
7. Severe hepatic and renal impairment as no safety and PK data of isoquercetin are available in these populations.
8. Current daily use of aspirin (> 81 mg daily), Clopidogrel (Plavix), cilostazol (Pletal), aspirin-dipyridamole (Aggrenox) (within 10 days) or considered to use regular use of higher doses of non-steroidal anti-inflammatory agents as determined by the treating physician (e.g. ibuprofen > 800 mg daily or equivalent).
9. Concomitant use of Cyclosporine, Warfarin (Coumarin), TPA, strong inducer of CYP3A4, or substrate of CYP3A4 with narrow therapeutic index.
10. History of allergic reactions attributed to compounds of similar chemical or biologic composition to isoquercetin.
11. Pregnancy.
12. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with isoquercetin, breastfeeding should be discontinued if the mother is treated with Isoquercetin. These potential risks may also apply to other agents used in this study.
13. Known hypersensitivity to Isoquercetin, Quercetin, or to any of the excipients used in the Isoquercetin capsules.
14. Patient with history of poor compliance, or current or past psychiatric disease that might interfere with the ability to comply with the study procedures or give informed consent according to the judgment of the investigator or institutionalized by court decision.
15. Patient with any condition that the physician judges could be detrimental to patient participating in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control arm; In this arm subjects will receive the hospital COVID-19 standard care	Drug: Hospital standard of care for COVID-19; Standard care for COVID-19 as per the hospital guidelines
Experimental: Isoquercetin arm; In this arm subjects will receive the hospital COVID-19 standard care + Isoquercetin	Drug: Hospital standard of care for COVID-19; Standard care for COVID-19 as per the hospital guidelines; Drug: Isoquercetin; Daily 1000 mg Isoquercetin as 4 capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Disease progression, defined as WHO Clinical Progression Scale score of ≥ 6, at any time from day 1 to day 28	From day 1 to day 28

Secondary Outcome Measures

Outcome Measure	Time Frame
Disease recovery, defined as WHO Progression Scale score of ≤ 2, at day 28	Day 1 through Day 28

Other Outcome Measures

Outcome Measure	Time Frame
Change in the WHO Progression Scale score from baseline	Day 1 through Day 28
Changes in daily breathlessness, cough and sputum scale (BCSS) score (including disaggregated scores)	Day 1 through Day 28
Percentage of patients who progress to require mechanical ventilation	Day 1 through Day 28
Percentage of patients admitted to intensive care unit admission	Day 1 through Day 28
Time to recovery	Day 1 through Day 28
Time to hospital discharge	Day 1 through Day 28
Change in National Early Warning Score (NEWS 2) from baseline	Day 1 through Day 28
All-cause mortality	Day 1 through Day 28
QoL (EQ-5D-5L respiratory questionnaire)	Day 1 through Day 28

Collaborators and Investigators

• Sponsor: Nepal Health Research Council

Study record dates

Study Major Dates

• Study Start (Anticipated): February 20, 2021
• Primary Completion (Anticipated): May 20, 2021
• Study Completion (Anticipated): August 15, 2021

Study Registration Dates

• First Submitted: January 31, 2021
• First Submitted That Met QC Criteria: February 1, 2021
• First Posted (Actual): February 2, 2021

Study Record Updates

• Last Update Posted (Actual): February 5, 2021
• Last Update Submitted That Met QC Criteria: February 2, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: 22-2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No