Clinical trial NCT04768179: Safety & Efficacy of Low Dose Aspirin / Ivermectin Combination Therapy for Treatment of Covid-19 Patients
Official title: A Randomized Clinical Trial to Investigate Safety & Efficacy of Low-dose Aspirin / Ivermectin Combination Therapy in Management of COVID-19 Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Covid19
Keywords: COVID-19 Therapies
Lead sponsor: Makerere University
Sponsor class: OTHER
Collaborators: name: Ministry of Health, Uganda
name: Mbarara University of Science and Technology
name: Joint Clinical Research Center
First posted: 2021-02-24
Enrollment: 490
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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
* 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

Primary outcomes:
measure: SARS COV 2 Viral clearance
timeFrame: Day 14
measure: World Health Organization COVID-19 ordinal improvement score
timeFrame: Day 14
Secondary outcomes:
measure: Clinical recovery
timeFrame: Day 14
measure: Spectrum and severity of adverse events
timeFrame: Days one to day 14
measure: Maximum Plasma concentration
timeFrame: Days one to six
measure: Minimum Plasma concentration
timeFrame: Days one to six
measure: Area Under the Curve
timeFrame: Days one to six
Other outcomes:
Locations:
Study officials:
affiliation: Makerere University, college of Health Sciences
name: Jackson Mukonzo, PhD
role: PRINCIPAL_INVESTIGATOR
References: