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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Covid19

Intervention / Treatment
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* Drug: 3-dayIVM 200 mcg/kg/day/14-day 75mgASA/day + standard of care (intervention 1)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19 Therapies