A Randomized Clinical Trial to Investigate Safety & Efficacy of Low-dose Aspirin / Ivermectin Combination Therapy in Management of COVID-19 Patients
Overview
- Phase
- Phase 2
- Intervention
- 3-dayIVM 200 mcg/kg/day/14-day 75mgASA/day + standard of care (intervention 1)
- Conditions
- Covid19
- Sponsor
- Makerere University
- Enrollment
- 490
- Primary Endpoint
- SARS COV 2 Viral clearance
- Last Updated
- 5 years ago
Overview
Brief Summary
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
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.
Investigators
College of Health Sciences
Chair and Associate professor Department of Pharmacology and Therapeutics
Makerere University
Eligibility Criteria
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
Exclusion Criteria
- Not provided
Arms & Interventions
Arm 2
Drug: 3-dayIVM 200 mcg/kg/day/14-day 75mgASA/day + standard of care (intervention 1)
Intervention: 3-dayIVM 200 mcg/kg/day/14-day 75mgASA/day + standard of care (intervention 1)
Arm 3
3-day Ivermectin 600 mcg/kg/day/14-day 75mgASA/day + standard of care (Intervention 2)
Intervention: 3-dayIVM 200 mcg/kg/day/14-day 75mgASA/day + standard of care (intervention 1)
Outcomes
Primary Outcomes
SARS COV 2 Viral clearance
Time Frame: Day 14
SARS COV 2 Viral load
World Health Organization COVID-19 ordinal improvement score
Time Frame: Day 14
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
Secondary Outcomes
- Spectrum and severity of adverse events(Days one to day 14)
- Clinical recovery(Day 14)
- Maximum Plasma concentration(Days one to six)
- Minimum Plasma concentration(Days one to six)
- Area Under the Curve(Days one to six)