Covid19Phase 3NCT04937569
Ivermectin Versus Standard Treatment in Mild COVID-19
A Phase 3 study testing Ivermectin Tablets in people with Covid19, run by Assiut University at 1 site in Egypt.
Trial summary
Rationale: Ivermectin, an inexpensive and available antiparasitic drug, with favourable safety profile, showed inhibitory effect on SARS-CoV2 viral replication in-vitro and in animal models. Several research groups investigated Ivermectin in COVID-19, particularly in mild symptomatic disease. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Covid19
- What is being tested?
- Ivermectin Tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,644 participants
- Where
- 1 siteEgypt
- Study dates
- 1 Jul 2021to 1 Nov 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed mild cases of COVID-19 defined as: symptomatic patients with any of COVID-19 symptoms (fever, cough, sore throat, malaise, headache, muscle pain, nausea, vomiting, diarrhea, loss of taste and smell),
- In addition to absolute leucopoenia (< 4000) / absolute lymphopenia (< 1000), positive CRP (C-reactive protein), high serum ferritin and/or positive PCR for SARS-CoV-2 in nasopharyngeal swab.
- no dyspnea and no abnormalities on high resolution chest imaging (HRCT).
- Patients should be at home (not admitted to hospital) with no supplemental oxygen treatment.
Who cannot join
- • Asymptomatic patients
- Dyspnoea or abnormalities on chest imaging
- Hospital admission
- Severe pneumonia
- Impairment in liver functions
- Received Ivermection in the last 5 days before being included in the study.
- Pregnancy is an exclusion criterion
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Ivermectin Versus Standard Treatment in Mild COVID-19: a Prospective Cohort Study.
Rationale: Ivermectin, an inexpensive and available antiparasitic drug, with favourable safety profile, showed inhibitory effect on SARS-CoV2 viral replication in-vitro and in animal models. Several research groups investigated Ivermectin in COVID-19, particularly in mild symptomatic disease. There is high degree of uncertainty on its effects on clinical outcomes and larger studies are needed.
Objectives: Plan to study the effect of Ivermectin versus standard treatment in patients with confirmed mild COVID-19.
Read more
Study design: Multi-centre prospective cohort study Settings: Assiut University Hospital (Assiut University), Aswan and others, Egypt.
Study Population: Patients with confirmed mild COVID-19. Intervention: Patients with mild symptomatic COVID-19 attending the participating out-patient clinics in different centers will receive either Ivermectin + Standard treatment or Standard treatment only. All new mild symptomatic COVID-19 patients will receive Ivermectin + Standard treatment for the first two weeks of the study. During the following four weeks, all new patients will receive standard treatment only. These cycles will be repeated until 822 patients are recruited in each arm. Patients assigned to Ivermectin + Standard treatment or standard treatment only will remain as such throughout the study and during the follow- up period.
Primary outcome measures: The primary outcome will be rate of intensive care admission.
Secondary outcome measures: Secondary outcomes will be time to clinical improvement, the clinical state using 7-point ordinal scale at different time points, need for home oxygenation, hospitalization, hospital supplemental oxygen >24 hours, Non- invasive ventilation ( High- flow nasal cannula, High- velocity nasal insufflation or BiPAP), duration of hospitalization, duration of ICU stay and deaths within 21 days,.
Power calculation:
With a prospective cohort design, a sample size of 822 cases per group is estimated (1644 for the whole study). This calculation depends on a rate of ICU admission in mild symptomatic COVID-19 cases of 8.5%, an assumption that Ivermectin can reduce this rate by 50%, at a study power of 80%, and confidence limit of 0.95.
Read the detailed description
- Introduction and rationale: An outbreak of atypical pneumonia of unknown cause erupted in Wuhan, China in December 2019. The symptoms ranged from mild symptoms to severe acute respiratory distress syndrome, with multi-organ affection leading to patients' death. Within few weeks, genetic sequence of the causative virus was identified to be close to Severe Acute Respiratory Distress Virus (SARS-CoV) (Zhou et al, 2020). The newly identified virus was named Novel Coronavirus or SARS-CoV2, and the clinical disease as COVID-19 (Chung et al, 2021). The disease spread rapidly with travel movements around the world and the World Health organization announced the COVID-19 as a pandemic on March 11th, 2020 (Cucinotta and Vanelli, 2020). The worldwide disease toll approached more the 165 million confirmed cases including more than 3.5 million deaths as of May 21st, 2021, making it the worst pandemic in the last 100 years [WHO Coronavirus (COVID-19) Dashboard].
Attempting to find therapeutic options for COVID-19, viral inhibitor drugs that have been used against influenza and HIV, were repurposed to be tested against SARS-CoV2. These include Chloroquine/ Hydroxychloroquine which inhibit viral entry and endocytosis in vitro, protease inhibitors Lopinavir-Ritonavir which disrupt viral replication in-vitro, and RNA dependent polymerase inhibitors including Ribavirin, Favipiravir and Remdesivir (Wiersinga et al, 2020). Only Remdesivir showed initial promising results in a randomized clinical trial (Beigel et al, 2020), however, currently the World Health Organization recommends against its use in any disease severity (Lamontage et al, 2021).
Ivermectin is an inexpensive and available antiparasitic drug, with favourable safety profile. It showed inhibitory effect on SARS-CoV2 viral replication in vitro and in animal models (Formiga et al, 2021). Several research groups investigated Ivermectin in COVID-19, particularly early in mild disease where viral replication is more active (Kory et al, 2021). In its living guideline on drugs used to treat COVID-19, the WHO recommended against the use of Ivermectin in COVID-19, regardless of duration of symptoms or disease severity, except in the contest of clinical trials. The reason was high degree of uncertainty about clinical outcomes of importance to the patients like time to clinical improvement, hospital admission, duration of hospitalization, mechanical ventilation and mortality. The WHO recommends larger and well-designed studies to solve this uncertainty (Lamontage et al, 2021).
In the present study protocol, the investigators plan to study the effect of Ivermectin versus standard treatment in patients with confirmed mild symptomatic COVID-19. The primary outcome will be rate of intensive care admission. Secondary outcomes will be time to clinical improvement, patient's clinical state using 7-point ordinal scale at different time points, proportion of subjects needing hospitalization, supplemental oxygen >24 hours, duration of hospitalization, duration of ICU stay or death within 21 days.
- Conditions
- Covid19
- Being tested
- Ivermectin Tablets
- Keywords
- COVID-19, Ivermectin, Standard therapy, ICU admission, Clinical improvement, Side effects, Effectiveness
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ivermectin TabletsDrug
4-days course of Ivermectin 400 microgram/kg body weight maximum 4 tablets (6mg / tablet) once daily dose before breakfast
| Study group | Role | What they receive |
|---|---|---|
| Group 1: Ivermectin + standard treatment | Active comparator | Patients will receive 4-days course of Ivermectin 400 microgram/kg body weight maximum 4 tablets (6mg / tablet) once daily dose before breakfast plus standard treatment (Azithromycin 500mg once daily for 5 days, Paracetamol 500mg every 8 hours, vitamin C 1gm once daily, Zinc 50 mg once daily, Lactoferrin 100mg sachets twice daily and prophylactic or therapeutic anticoagulation if D-dimer is elevated. Receives: Drug: Ivermectin Tablets |
| Group-2: Standard treatment only | Other | This group will receive the standard treatment protocol as outlined above according to the Egyptian Ministry of Health protocol of treating cases with mild COVID-19. Receives: Drug: Ivermectin Tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of ICU admission in mild COVID-19 cases
Indications of ICU admission, Respiratory rate (RR) > 30 cycle/min, Oxygen saturation < 92% at room air, PaO2/FiO2 ratio < 300, Chest radiography showing more than 50% lung lesions, or progressive lesions within 24-48 hours, Critically ill if RR > 30, Oxygen saturation < 92%, or PaO2/FiO2 ratio < 200 despite oxygen therapy.
Measured: 21 days
Secondary outcomes (4)
Time to clinical improvement.
days to fever, dyspnea, cough improvement
Measured: 21 days
Overall clinical state, using the 7-point ordinal scale
7-point ordinal scale is: 1. Death 2. Hospitalized, on invasive mechanical ventilation or Extracorporeal Membrane Oxygenation 3. Hospitalized, on non-invasive ventilation or high flow oxygen 4. Hospitalized, requiring low flow supplemental oxygen 5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) 6. Hospitalized, not requiring supplemental oxygen - no longer required ongoing medical care 7. Not hospitalized.
Measured: 21 days
The duration of critical care interventions in each arm of the study.
- The duration of supplemental oxygen in each arm of the study.
- The duration of hospitalization in each arm of the study.
- The duration of stay in the ICU in each arm of the study.
Measured: 21 Days
• Proportion of subjects who develop adverse events associated with the study drug.
percentage of patients having SE as headache, dizziness, diarrhoea, nausea, disturbed vision, tremors, skin discoloration, skin rash, swelling, vomiting
Measured: 21 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2021
- Study start1 Jul 2021 (estimated)
- Primary completion1 Sep 2021 (estimated)
- Study completion1 Nov 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Covid19Studies of the same condition, open and under way.
- More trials run by Assiut UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 1,644 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Aliae AR Mohamed Hussein, Assiut University
- Investigators
- Aliae AR Mohamed-Hussein, MD, Principal investigator, Assiut UniversityEssam R Othman, MD, Study director, Assiut UniversityBen WJ Mol, MD, Study chair, Monash University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04937569
- Sponsor's protocol ID
- AssiutU-Ivercom
- Status last verified
- Jun 2021
- First submitted
- 23 Jun 2021
- Last updated
- 29 Jun 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ivermectin Versus Standard Treatment in Mild COVID-19: a Prospective Cohort Study.
- ClinicalTrials.gov ID
- NCT04937569
- Acronym / sponsor ID
- AssiutU-Ivercom
- Conditions
- Covid19
- Keywords
- COVID-19, Ivermectin, Standard therapy, ICU admission, Clinical improvement, Side effects, Effectiveness
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 1,644 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- 1 Jul 2021 (estimated)
- Primary completion
- 1 Sep 2021 (estimated)
- Study completion
- 1 Nov 2021 (estimated)
- First posted
- 24 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Rationale: Ivermectin, an inexpensive and available antiparasitic drug, with favourable safety profile, showed inhibitory effect on SARS-CoV2 viral replication in-vitro and in animal models. Several research groups investigated Ivermectin in COVID-19, particularly in mild symptomatic disease. There is high degree of uncertainty on its effects on clinical outcomes and larger studies are needed.
Objectives: Plan to study the effect of Ivermectin versus standard treatment in patients with confirmed mild COVID-19.
Study design: Multi-centre prospective cohort study Settings: Assiut University Hospital (Assiut University), Aswan and others, Egypt.
Study Population: Patients with confirmed mild COVID-19. Intervention: Patients with mild symptomatic COVID-19 attending the participating out-patient clinics in different centers will receive either Ivermectin + Standard treatment or Standard treatment only. All new mild symptomatic COVID-19 patients will receive Ivermectin + Standard treatment for the first two weeks of the study. During the following four weeks, all new patients will receive standard treatment only. These cycles will be repeated until 822 patients are recruited in each arm. Patients assigned to Ivermectin + Standard treatment or standard treatment only will remain as such throughout the study and during the follow- up period.
Primary outcome measures: The primary outcome will be rate of intensive care admission.
Secondary outcome measures: Secondary outcomes will be time to clinical improvement, the clinical state using 7-point ordinal scale at different time points, need for home oxygenation, hospitalization, hospital supplemental oxygen >24 hours, Non- invasive ventilation ( High- flow nasal cannula, High- velocity nasal insufflation or BiPAP), duration of hospitalization, duration of ICU stay and deaths within 21 days,.
Power calculation:
With a prospective cohort design, a sample size of 822 cases per group is estimated (1644 for the whole study). This calculation depends on a rate of ICU admission in mild symptomatic COVID-19 cases of 8.5%, an assumption that Ivermectin can reduce this rate by 50%, at a study power of 80%, and confidence limit of 0.95.
Detailed description
- Introduction and rationale: An outbreak of atypical pneumonia of unknown cause erupted in Wuhan, China in December 2019. The symptoms ranged from mild symptoms to severe acute respiratory distress syndrome, with multi-organ affection leading to patients' death. Within few weeks, genetic sequence of the causative virus was identified to be close to Severe Acute Respiratory Distress Virus (SARS-CoV) (Zhou et al, 2020). The newly identified virus was named Novel Coronavirus or SARS-CoV2, and the clinical disease as COVID-19 (Chung et al, 2021). The disease spread rapidly with travel movements around the world and the World Health organization announced the COVID-19 as a pandemic on March 11th, 2020 (Cucinotta and Vanelli, 2020). The worldwide disease toll approached more the 165 million confirmed cases including more than 3.5 million deaths as of May 21st, 2021, making it the worst pandemic in the last 100 years [WHO Coronavirus (COVID-19) Dashboard].
Attempting to find therapeutic options for COVID-19, viral inhibitor drugs that have been used against influenza and HIV, were repurposed to be tested against SARS-CoV2. These include Chloroquine/ Hydroxychloroquine which inhibit viral entry and endocytosis in vitro, protease inhibitors Lopinavir-Ritonavir which disrupt viral replication in-vitro, and RNA dependent polymerase inhibitors including Ribavirin, Favipiravir and Remdesivir (Wiersinga et al, 2020). Only Remdesivir showed initial promising results in a randomized clinical trial (Beigel et al, 2020), however, currently the World Health Organization recommends against its use in any disease severity (Lamontage et al, 2021).
Ivermectin is an inexpensive and available antiparasitic drug, with favourable safety profile. It showed inhibitory effect on SARS-CoV2 viral replication in vitro and in animal models (Formiga et al, 2021). Several research groups investigated Ivermectin in COVID-19, particularly early in mild disease where viral replication is more active (Kory et al, 2021). In its living guideline on drugs used to treat COVID-19, the WHO recommended against the use of Ivermectin in COVID-19, regardless of duration of symptoms or disease severity, except in the contest of clinical trials. The reason was high degree of uncertainty about clinical outcomes of importance to the patients like time to clinical improvement, hospital admission, duration of hospitalization, mechanical ventilation and mortality. The WHO recommends larger and well-designed studies to solve this uncertainty (Lamontage et al, 2021).
In the present study protocol, the investigators plan to study the effect of Ivermectin versus standard treatment in patients with confirmed mild symptomatic COVID-19. The primary outcome will be rate of intensive care admission. Secondary outcomes will be time to clinical improvement, patient's clinical state using 7-point ordinal scale at different time points, proportion of subjects needing hospitalization, supplemental oxygen >24 hours, duration of hospitalization, duration of ICU stay or death within 21 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1: Ivermectin + standard treatment | Active comparator | Drug: Ivermectin TabletsPatients will receive 4-days course of Ivermectin 400 microgram/kg body weight maximum 4 tablets (6mg / tablet) once daily dose before breakfast plus standard treatment (Azithromycin 500mg once daily for 5 days, Paracetamol 500mg every 8 hours, vitamin C 1gm once daily, Zinc 50 mg once daily, Lactoferrin 100mg sachets twice daily and prophylactic or therapeutic anticoagulation if D-dimer is elevated. |
| Group-2: Standard treatment only | Other | Drug: Ivermectin TabletsThis group will receive the standard treatment protocol as outlined above according to the Egyptian Ministry of Health protocol of treating cases with mild COVID-19. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Confirmed mild cases of COVID-19 defined as: symptomatic patients with any of COVID-19 symptoms (fever, cough, sore throat, malaise, headache, muscle pain, nausea, vomiting, diarrhea, loss of taste and smell),
- In addition to absolute leucopoenia (< 4000) / absolute lymphopenia (< 1000), positive CRP (C-reactive protein), high serum ferritin and/or positive PCR for SARS-CoV-2 in nasopharyngeal swab.
- no dyspnea and no abnormalities on high resolution chest imaging (HRCT).
- Patients should be at home (not admitted to hospital) with no supplemental oxygen treatment.
Key exclusion criteria (7 listed)
- • Asymptomatic patients
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ivermectin Tablets4-days course of Ivermectin 400 microgram/kg body weight maximum 4 tablets (6mg / tablet) once daily dose before breakfast | Drug | Group 1: Ivermectin + standard treatment, Group-2: Standard treatment only |
Primary outcome
Rate of ICU admission in mild COVID-19 cases
Time frame: 21 days
Indications of ICU admission, Respiratory rate (RR) > 30 cycle/min, Oxygen saturation < 92% at room air, PaO2/FiO2 ratio < 300, Chest radiography showing more than 50% lung lesions, or progressive lesions within 24-48 hours, Critically ill if RR > 30, Oxygen saturation < 92%, or PaO2/FiO2 ratio < 200 despite oxygen therapy.
4 secondary outcomes
Time to clinical improvement.
Time frame: 21 days
Overall clinical state, using the 7-point ordinal scale
Time frame: 21 days
The duration of critical care interventions in each arm of the study.
Time frame: 21 Days
• Proportion of subjects who develop adverse events associated with the study drug.
Time frame: 21 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Aliae AR Mohamed-Hussein, MD principal investigator
Assiut University
Essam R Othman, MD study director
Assiut University
Ben WJ Mol, MD study chair
Monash University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ivermectin Tablets in people with Covid19, run by Assiut University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 29 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Aliae AR Mohamed-Hussein, MD (01222302352, aliaehussein@aun.edu.eg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of ICU admission in mild COVID-19 cases (time frame: 21 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2021.