Safety & Efficacy of Low Dose Aspirin / Ivermectin Combination Therapy for Treatment of Covid-19 Patients (IVCOM)

A Randomized Clinical Trial to Investigate Safety & Efficacy of Low-dose Aspirin / Ivermectin Combination Therapy in Management of COVID-19 Patients

COVID-19, caused by the novel Severe Acute Respiratory Syndrome Corona Virus 2 (SARSCoV-2), has become a global pandemic. Fortunately, most of the COVID-19 cases confirmed are categorized as mild for whom home- based symptomatic management with monitoring of clinical deterioration is recommended. Despite providing symptomatic management, a therapeutic drug that would limit the course of infection is greatly needed to stop COVID-19 disease progression. Considering the current SARS-CoV-2 epidemiology and the legitimate rash towards appropriate therapies, our study seeks to evaluate the safety and efficacy of low dose aspirin and ivermectin combination therapy in COVID-19 patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Covid19
• Intervention / Treatment: Drug: 3-dayIVM 200 mcg/kg/day/14-day 75mgASA/day + standard of care (intervention 1)

Detailed Description

Micro clotting is to date reported as a major cause of death among COVID-19 patients. SARS-CoV-2 associated micro clotting results into acute respiratory distress syndrome (ARDS) and death. This micro-clotting cascade supports the potential role of anticoagulants like aspirin, heparin in the clinical management of COVID-19 patients. Other areas that could be considered for potential treatment of COVID-19 include drugs and analogues of drugs that have demonstrated potential in-vitro and or in-vivo activity against SARS-CoV-2 like hydroxychloroquine, azithromycin, lopinavir/ritonavir and remdesivir and ivermectin. Ivermectin has demonstrated broad-spectrum anti-viral activity and inhibition of the causative virus (SARS-CoV-2) with ability to cause a 5000-fold reduction in viral RNA within 48hrs.

Although aspirin and ivermectin do not exhibit any synergistic or potentiation at cellular level, a clinical additive effect resulting from combination therapy with low dose aspirin and ivermectin is plausible. There is no documented drug-drug interactions or other biological basis that contra-indicate co-administration of low dose aspirin and ivermectin.

We therefore propose, to explore the clinical use of combination anticoagulant: lower dose aspirin and the FDA-approved anti-parasitic drug: ivermectin, in treatment of COVID-19 patients in an exploratory randomized trial.

• Study Type: Interventional
• Enrollment (Anticipated): 490
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Jackson Mukonzo, PhD; Phone Number: 256758113468; Email: mukojack@yahoo.co.uk
• Study Contact Backup: Name: Rita Nakato, MSc; Email: nakato.ritah@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Provision of signed and dated informed consent form
• Willingness to comply with all study procedures and availability over the study duration *Patients aged above 18years to 64 years
• PCR positive for SARS-Cov-2 (COVID-19) from any of the MOH COVID-19 accredited testing laboratories
• Moderately ill COVID-19 patients score 3(Hospitalized with no oxygen therapy) to 4 (Hospitalized with oxygen by mask or nasal prongs) according to the WHO ordinal scale for clinical improvement which translates to moderate to severe COVID-19 patients according to the Ministry of Health Uganda COVID-19 disease category.

Exclusion criteria:

• Participants with known hypersensitivity to Ivermectin
• Clinical diagnosis of severe renal and hepatic impairment.
• Pregnancy or breast feeding.
• Co-treatment with either strong cytochrome p-450 inducers including: rifampicin, carbamazepine and barbiturates or inhibitors: isoniazid, clofazimine that might potentially affected ivermectin disposition and clinical outcomes
• Co-morbidities including asthma
• Loa loa as assessed by travel history to Angola, Cameroon, Chad, Central African Republic, Congo, DR Congo, Equatorial Guinea, Ethiopia, Gabon, Nigeria and Sudan in the last 4 years
• Persons clinically diagnosed with and receiving treatment for any diathesis and PUD
• Active participation in another clinical trial

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Arm1 (Control group); standard of care
Experimental: Arm 2; Drug: 3-dayIVM 200 mcg/kg/day/14-day 75mgASA/day + standard of care (intervention 1)	Drug: 3-dayIVM 200 mcg/kg/day/14-day 75mgASA/day + standard of care (intervention 1); Low dose aspirin for 14 days plus ivermectin at 200 mcg/kg/day or 600 mcg/kg/day for 3 days; Other Names: 3-dayIVM 600 mcg/kg/day/14-day 75mgASA/day + standard of care (intervention 2)
Experimental: Arm 3; 3-day Ivermectin 600 mcg/kg/day/14-day 75mgASA/day + standard of care (Intervention 2)	Drug: 3-dayIVM 200 mcg/kg/day/14-day 75mgASA/day + standard of care (intervention 1); Low dose aspirin for 14 days plus ivermectin at 200 mcg/kg/day or 600 mcg/kg/day for 3 days; Other Names: 3-dayIVM 600 mcg/kg/day/14-day 75mgASA/day + standard of care (intervention 2)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SARS COV 2 Viral clearance	SARS COV 2 Viral load	Day 14
World Health Organization COVID-19 ordinal improvement score	Minimum score is 0 (un infected, no clinical or virological evidence of infection) Maximum sore is 8 (death) Higher scores mean a worse outcome, low scores mean a better outcome	Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical recovery	disappearance or cessation of COVID-19 associated symptoms	Day 14
Spectrum and severity of adverse events	Adverse drug reactions	Days one to day 14
Maximum Plasma concentration	average maximum ivermectin drug concentrations	Days one to six
Minimum Plasma concentration	average minimum drug concentrations	Days one to six
Area Under the Curve	Population drug concentrations from time of the first drug administration to the time when the last dose is eliminated	Days one to six

Collaborators and Investigators

• Sponsor: Makerere University
• Collaborators: Mbarara University of Science and Technology; Ministry of Health, Uganda; Joint Clinical Research Center
• Investigators: Principal Investigator: Jackson Mukonzo, PhD, Makerere University, College Of Health Sciences

Study record dates

Study Major Dates

• Study Start (Anticipated): February 19, 2021
• Primary Completion (Anticipated): June 30, 2021
• Study Completion (Anticipated): September 30, 2021

Study Registration Dates

• First Submitted: February 14, 2021
• First Submitted That Met QC Criteria: February 23, 2021
• First Posted (Actual): February 24, 2021

Study Record Updates

• Last Update Posted (Actual): February 24, 2021
• Last Update Submitted That Met QC Criteria: February 23, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: COVID-19 Therapies
• 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: IVCOM PROTOCOL VERSION 03

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No