Efficacy and Safety of Ivermectin for Treatment and Prophylaxis of COVID-19 Pandemic

Benha University

Status: Completed

Conditions: Covid19

Treatments: Drug: Hydroxychloroquine; Drug: Ivermectin; Behavioral: personal protective Measures

Study type: Interventional

Funder types: Other

Identifiers

NCT04668469

Re96.2020

Details and patient eligibility

About

Background: Up-to-date, there is no recognized effective treatment or vaccine for the treatment of coronavirus disease (COVID-19) that emphasize urgency around distinctive effective therapies. This study aims to evaluate the anti-parasitic medication efficacy "Ivermectin" plus standard care (Azithromycin, Paracetamol, vitamin C, Zinc, Lactoferrin, Acetylcystein, prophylactic or therapeutic anticoagulation if D-dimer > 1000 and/or steroids) in the treatment of mild/moderate and severely ill cases with COVID 19 infection versus Hydroxychloroquine plus standard care, as well as Ivermectin prophylaxis of health care and/ or household contacts.

Subject and methods: 600 subjects; 400 symptomatic confirmed COVID-19 patients and 200 health care and household contacts distributed over 6 groups; Group I: 100 patients with Mild/Moderate COVID-19 infection received a 4-days course of Ivermectin plus standard care; Group II: 100 patients with mild/moderate COVID-19 infection received hydroxychlorquine plus standard care; Group III: 100 patients with severe COVID-19 infection received Ivermectin plus standard of care; Group IV: 100 patients with Severe COVID-19 infection received hydroxychlorquine plus standard care. Routine laboratory investigations and real time- polymerase chain reaction (rt-PCR) were reported before and after initiation of treatment. Group V stick to personal protective equipment (PPE) plus Ivermectin, and Group VI stick to PPE only and both groups were followed for two weeks.

Full description

I-Technical design:

Study design: interventional multicenter double blind randomized controlled clinical trial (RCCT) study Study period: The study was carried out from 8th June to 15th September 2020.

*Study population (Sampling Design and Sample Size):

The study was conducted on 600 subjects; 400 patients and 200 health care and household contacts that were divided into 6 groups:

• Group I: 100 patients with Mild/Moderate COVID-19 infection received a 4-days course of Ivermectin 400 mcg/kg body weight maximum 4 tablets (6mg / tablet) once daily dose before breakfast plus standard care as issued by Egyptian protocol of COVID-19 treatment (Azithromycin 500mg once daily/5days, Paracetamol 500mg as needed, vitamin C 1gm once daily, Zinc 50 mg once daily, Lactoferrin 100mg sachets/12 hours & Acetylcystein 200mg/8hours & prophylactic or therapeutic anticoagulation if D-dimer > 1000), (MOH version 30 May 2020).
• Group II: 100 patients with mild/moderate COVID-19 infection received hydroxychlorquine (400 every 12 hours for one day followed by 200 mg every 12 hours for 5 days) plus standard care (Azithromycin 500mg once daily/5days, Paracetamol 500mg as needed, vitamin C 1gm once daily, Zinc 50 mg once daily, Lactoferrin 100mg sachets /12 hours & Acetylcystein 200mg sachets /8 hours & prophylactic or therapeutic anticoagulation if D-dimer > 1000) as issued by Egyptian protocol of COVID-19 treatment.
• Group III: 100 patients with severe COVID-19 infection received a 4 days course of Ivermectin 400 mcg/kg body weight maximum 4 tablets (6mg / tablet) once daily dose before breakfast plus standard care (Azithromycin 500mg once daily/5days, Paracetamol 500mg as needed, vitamin C 1gm once daily, Zinc 50 mg once daily, Lactoferrin 100mg sachets/ 12 hours & Acetylcystein 200mg sachets/ 8 hours & prophylactic or therapeutic anticoagulation if D-dimer > 1000) as issued by Egyptian protocol of COVID-19 treatment for severe patients.
• Group IV: 100 patients with Severe COVID-19 infection received hydroxychlorquine (400 mg every 12 hours for one day followed by 200 mg every 12 hours for 9 days) plus standard care (Azithromycin 500mg once daily/5days, Paracetamol 500mg as needed, vitamin C 1gm once daily, Zinc 50 mg once daily, Lactoferrin 100mg/12 hours & Acetylcystein 200mg sachets/ 8 hours & prophylactic or therapeutic anticoagulation if D-dimer > 1000) as issued by Egyptian protocol of COVID-19 treatment for severe ill patients.
• Group V: 100 health care and or household patients' contacts received a prophylactic dose of ivermectin 400 micrograms/kg single oral dose before breakfast to be repeated after one week in addition to PPE (personal protective equipment).
• Group VI: 100 health care and or household patients' contacts received only PPE (personal protective equipment).

Study methods and Tools:

All patients were subjected to:

• Full history and clinical examination taking, and laboratory assessment including liver function tests, kidney function tests, full blood count, serum Ferritin level. C-reactive protein (CRP), D-dimer, rt- PCR for COVID-19 and, radiological assessments including CT chest.
• Follow up: Patients were followed up daily clinically and by laboratory assessment for two weeks but radiological assessment after two weeks or until one of the endpoints is reached. Follow up the duration of treatment, swab conversion, hospital stay, the clinical and radiological improvement was recorded.

Enrollment: 600 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria: Patients who have been diagnosed with COVID-19 infection with at least one positive rt-PCR result from nasopharyngeal/oropharyngeal swab, then subdivided patients into mild, moderate and sever stages.

Exclusion criteria:

• Pregnancy and lactation, and critical cases defined as: occurrence of respiratory failure requiring mechanical ventilation; Presence of shock; other organ failure that requires monitoring and treatment in the ICU, [20].
• Patients with hydroxychloroquine contra-indications: corrected QT interval (QTc) > 500 m/sec, myasthenia gravis, porphyria, retinal pathology, epilepsy, glucose-6-phosphate dehydrogenase (G6PD) deficiency, allergy to 4-aminoquinolone, chronic heart, kidney or liver disease, and arrhythmias.
• Any patient demonstrates worsening of symptoms; radiological progression with virologically persistence within at least 7 days of the therapeutic evaluation period of the study after exclusion of cytokine storm was considered as a clinical failure and was shifted to the other management protocol.
• Treatment was terminated at any time by a multidisciplinary team if a serious side effect occurred, which was attributed to the medications used ,e.g. cardiac arrhythmia, deteriorated liver or kidney function or unfortunately patient died.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

---

600 participants in 6 patient groups

Ivermectin plus standard care in Mild/Moderate COVID-19 (Group I)

Experimental group

Description:

100 patients with Mild/Moderate COVID-19 (Coronavirus disease) infection received a 4-days course of Ivermectin 400 mcg/kg body weight maximum 4 tablets (6mg / tablet) once daily dose before breakfast plus standard of care as issued by Egyptian protocol of COVID-19 treatment.

Treatment:

Drug: Ivermectin

hydroxychlorquine plus standard care in Mild/Moderate COVID-19 (Group II)

Active Comparator group

Description:

100 patients with mild/moderate COVID-19 infection received hydroxychlorquine (400 every 12 hours for one day followed by 200 mg every 12 hours for 5 days) plus standard care.

Treatment:

Drug: Hydroxychloroquine

Ivermectin plus standard care and steroids in Sever COIVD-19 (Group III)

Experimental group

Description:

100 patients with severe COVID-19 infection received a 4 days course of Ivermectin 400 mcg/kg body weight maximum 4 tablets (6mg / tablet) once daily dose before breakfast plus standard care and steroids

Treatment:

Drug: Ivermectin

hydroxychlorquine plus standard care and steroids in Sever COVID-19 (Group IV)

Active Comparator group

Description:

100 patients with Severe COVID-19 infection received hydroxychlorquine (400 mg every 12 hours for one day followed by 200 mg every 12 hours for 9days) plus standard care and steroids

Treatment:

Drug: Hydroxychloroquine

Ivermectin plus personal protective measures in COVID-19 prophylaxis (Group V)

Experimental group

Description:

100 health care and or household contacts received a prophylactic dose of ivermectin 400 micrograms/kg single oral dose before breakfast to be repeated after one week in addition to Personal Protective Measures ( (hand hygiene, social distancing measures, avoiding touching the eyes, nose and mouth, Masks, respiratory etiquette, and self-isolation)

Treatment:

Behavioral: personal protective Measures

Drug: Ivermectin

Personal protective measures in COVID-19 prophylaxis (Group VI)

Active Comparator group

Description:

100 health care and or household contacts received only Personal Protective Measures (hand hygiene, social distancing measures, avoiding touching the eyes, nose and mouth, Masks, respiratory etiquette, and self-isolation)

Treatment:

Behavioral: personal protective Measures