COVID-19Phase 2IFCOVNCT05155527
Ivermectin With Favipiravir in Mild-to-moderate COVID-19 Patients
A Phase 2 study testing Ivermectin Tablets in people with COVID-19, run by Mahidol University at 2 sites in Thailand.
Trial summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are rapidly spreading worldwide and continue to be a global public health crisis. The use of repurposed drugs with the potential to inhibit SARS-CoV-2 could be a vital alternative approach when the novel therapeutic has not yet available. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- COVID-19
- What is being tested?
- Ivermectin Tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 200 participants
- Where
- 2 sitesThailand
- Study dates
- 10 Feb 2022to Jun 2022
- Phase
- Phase 2
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patient age between 18-65 years old
- Has confirmed SARS-CoV-2 infection by RT-PCR method using sample collected from nasopharyngeal swab (NP) and oropharyngeal swab (OP) with Ct value in either one of the following cases
- Ct ≤ 26 if the subject has RT-PCR performed as part of screening procedures
- Ct ≤ 24 if the subject has had RT-PCR performed before admission and the time between the sample collection for RT-PCR and randomization is ≤ 24 hours
- Has been admitted for medical care at the investigational sites
- In case of symptomatic patient, date of symptoms onset is ≤ 7 days prior to randomization. In case of asymptomatic patient, the first date of positive result from RT-PCR or antigen test kit for SARS-CoV-2 is ≤ 7 days prior to randomization.
Show all 12Show fewer
- Qualified for the criteria to receive favipiravir for COVID-19 treatment according to Guidelines on clinical practice, diagnosis, treatment, and prevention of healthcare-associated infection for COVID-19 in Thailand in either one of the following cases
- Will start receiving favipiravir during the study period or
- Has received favipiravir no more than 24 hours before receiving the investigational drug
- Asymptomatic or has mild to moderate COVID-19 as defined in section 7.2.2.
- Willing to participate in the study and able to provide written informed consent
- Women of childbearing potential must agree to either abstinence or use at least one primary form of contraception from the time of screening through D28.
Who cannot join
- Has severe or critical COVID-19 as defined in section 7.2.2.
- Bedridden (totally confined to bed)
- Has elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) over 3 times the upper range of normal limits, or history of liver cirrhosis
- Females only: Currently pregnant, as determined by positive β-human choriogonadotropin (HCG) test in urine, or breast-feeding
- Receiving other potential drugs for COVID-19 treatment prior to randomization including Remdesivir, Nitazoxanide, Chloroquine, Hydroxychloroquine, Azithromycin, Lopinavir-ritonavir, Famotidine, Tocilizumab, Baricitinib (except favipiravir)
- Received ivermectin within 1 month prior to the randomization
Show all 12Show fewer
- Receiving other immunosuppressive or immunomodulatory drugs for the treatment of other conditions (not including topical steroids)
- History of hypersensitivity to ivermectin or favipiravir or any components of the drugs
- Receiving medications that increase gamma-aminobutyric acid (GABA) potentiating activity such as barbiturates, benzodiazepines, sodium oxybate, valproic acid, or receiving medications that prevent or inhibit the p-glycoprotein transport system such as amiodarone, carvedilol, clarithromycin, cyclosporine, erythromycin, itraconazole, ketoconazole, quinidine, ritonavir, tamoxifen, verapamil, amprenavir, clotrimazole, phenothiazines, rifampin, St. John's Wort etc.
- Has history of hereditary xanthinuria
- Has hypouricemia (serum uric acid ≤ 1 mg/dL), uncontrolled gout or history of xanthine urolithiasis
- Participating in other clinical trials or participated in other clinical trials in a period of one month or less than 5 half-lives of the study drug before screening
Trial locations and contacts
2 sites in 1 country.
Thailand2 sites, 2 recruiting
- Recruiting
JC Kevin Sathorn Bangkok Hotel
Bangkok
Sanhapon Ketklao, MD, 0 2419 7000, sanhapon14@hotmail.com
- Recruiting
Songklanagarind Hospital
Bangkok
Saranyu Chusri, Assoc.prof, 0-7445-1483, sarunyouchusri@hotmail.com
About this study
Official title: A Phase 2 Double-blind Randomized Placebo-controlled Trial to Assess the Efficacy of Ivermectin in Combination With Favipiravir in Mild-to-moderate COVID-19 Adult Patients
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are rapidly spreading worldwide and continue to be a global public health crisis. The use of repurposed drugs with the potential to inhibit SARS-CoV-2 could be a vital alternative approach when the novel therapeutic has not yet available. The guidelines for emergency treatment of COVID-19 vary across different countries and largely rely on the off-label prescription of repurposed drugs. As a result, clinical studies to generate robust efficacy data for these repurposed drugs are warranted to effectively fight against the ongoing COVID-19 pandemic.
The broad spectrum antiparasitic drug ivermectin has previously been shown to exhibit broad antiviral activities against many RNA and DNA viruses. It has a reliable safety profile with comprehensive data for decades especially in mass drug administration programs for river blindness prophylaxis in several countries in Africa. Owing to its strong inhibitory activity against the replication of SARS-CoV-2 in vitro and its putative role in reducing cytokine storm, the drug has been repurposed to treat COVID-19 patients and has shown promising results in several clinical studies. Ivermectin has thus gained a considerable attention as a potential treatment for COVID-19. However, the National Institute of Health (NIH) and World Health Organization (WHO) currently state that studies on using ivermectin to treat COVID-19 patients remain inconclusive due to insufficient data. Therefore, a large well designed randomized, double blinded, placebo-controlled trial to assess the efficacy of ivermectin is urgently needed.
Read more
Another important treatment option for COVID-19 is favipiravir, an antiviral drug for influenza treatment. Although the drug has not been approved for a COVID-19 treatment by the US-FDA, it has been included in Guidelines on clinical practice, diagnosis, treatment, and prevention of healthcare-associated infection for COVID-19 in Thailand. Favipiravir, a known inhibitor of RNA-dependent RNA polymerase, was shown to have an in vitro activity against SARS-CoV-2. The meta-analysis showed a significant improvement in clinical outcome at day 14 along with chest imaging in the favipiravir group compared to standard care. However, there are no significant differences in terms of clinical deterioration rates, viral clearance, oxygen support requirement and side effect profiles. There are still ongoing clinical trials assessing the effectiveness of favipiravir in the treatment of COVID-19.
Antivirals can be generally divided into direct-acting antivirals (DAA) and host-targeting drugs. For example, the widely used drug remdesivir repurposed to treat COVID-19 is a DAA, and chloroquine is considered a host-targeting drug. Because these repurposed drugs were not specifically designed and developed for COVID-19, they are likely to be less efficacious, and partner drugs need to be further explored. Finding a right combination for DAA is a common practice for developing virus treatment regimens. Relying on different modes of action and absence of unfavorable drug interaction, the combinations are usually additive or synergistic. It is important to note that our in vitro data demonstrated the synergistic profile for the combination of favipiravir and ivermectin against SARS-CoV-2. It resulted in 4-fold reduction in the half maximal inhibitory concentration (IC50) as compared to individual drugs, from 1.2 µM to 0.3 µM with a peak Loewe synergy score of over 33.2 and a mean score of 18.8 (noted that Loewe synergy score > 10 indicates synergistic effect).
In response to this COVID-19 pandemic crisis, especially in a resource limited setting like Thailand, clinical studies to evaluate affordable and implementable interventions are a priority and are urgently needed. Ivermectin, a cheap and safe drug, has been widely used in humans for decades, and it has also demonstrated an inhibitory effect against SARS-CoV-2 in vitro. Here, we aim to conduct a multi-center, double-blind, randomized controlled trial in Thailand to reveal the effectiveness of ivermectin as a combination therapy with favipiravir (standard treatment) for COVID-19. The results of this study will provide much needed information for pursuing larger efficacy clinical trials to confirm whether the combination could be effectively used to treat COVID-19. Also, they could provide information on the rate of viral clearance, the primary endpoint of this study, which was proposed to be a predictive surrogate of clinical benefits and used as a proper endpoint in the phase II trials for candidate drug screening for COVID-19.
- Conditions
- COVID-19
- Being tested
- Ivermectin Tablets, Placebo
- Keywords
- COVID-19, Favipiravir, Ivermectin
- 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
6 mg/tablet
PlaceboOther
The placebo has same form as Ivermectin.
| Study group | Role | What they receive |
|---|---|---|
| Favipiravir plus Ivermectin | Experimental | Ivermectin 600 mcg/kg once daily for 5 days in combination with Favipiravir for 5-10 days (1,800 mg twice a day in day 1 then 800 mg twice a day for the other days. For BW > 90 kg: 2,400 mg twice a day in day 1 then 1,000 mg twice a day for the other days). Receives: Drug: Ivermectin Tablets |
| Favipiravir plus Placebo | Placebo comparator | Matching placebo once daily for 5 days in combination with Favipiravir for 5-10 days (1,800 mg twice a day in day 1 then 800 mg twice a day for the other days. For BW > 90 kg: 2,400 mg twice a day in day 1 then 1,000 mg twice a day for the other days). Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The rate of SARS-CoV-2 viral clearance
The rate of viral clearance as measured by Ct values from NP and OP swab once daily
Measured: Day 1- Day 6
Secondary outcomes (5)
Mortality rate
The proportion of subjects who died
Measured: Day 14 and Day 28
Progression to severe disease
The proportion of subjects with clinical deterioration by at least 2 points according to WHO ordinal scale for clinical improvement.
Measured: Day 1 to discharge Day, Day 14, Day 28
Duration of admission
Number of days of admission
Measured: Day 1 to discharge Day
Oxygen requirement
- The proportion of subjects who require the use of supplemental oxygen, non-invasive oxygen supplementation, mechanical ventilation, extracorporeal membrane oxygenation (ECMO) and admission to the intensive care unit (ICU)
- The duration that the subjects require the use of supplemental oxygen
Measured: Day 1 to Day 28
Proportions of SARS-CoV-2 viral clearance
The proportion of subjects with negative RT-PCR for SARS-CoV-2
Measured: Day 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2021
- Study start10 Feb 2022
- Primary completionJun 2022 (estimated)
- Study completionJun 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COVID-19Studies of the same condition, open and under way.
- More trials run by Mahidol 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mahidol University
- Sponsor type
- University, hospital or other
- Collaborators
- Prince of Songkla University
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05155527
- Sponsor's protocol ID
- CREC067/64BR-MED46
- Acronym
- IFCOV
- Status last verified
- Jun 2022
- First submitted
- 9 Dec 2021
- Last updated
- 8 Jun 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Double-blind Randomized Placebo-controlled Trial to Assess the Efficacy of Ivermectin in Combination With Favipiravir in Mild-to-moderate COVID-19 Adult Patients
- ClinicalTrials.gov ID
- NCT05155527
- Acronym / sponsor ID
- IFCOV / CREC067/64BR-MED46
- Conditions
- COVID-19
- Keywords
- COVID-19, Favipiravir, Ivermectin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Mahidol UniversityUniversity, hospital or other
- Collaborators
- Prince of Songkla University
- Study start
- 10 Feb 2022 (actual)
- Primary completion
- Jun 2022 (estimated)
- Study completion
- Jun 2022 (estimated)
- First posted
- 13 Dec 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.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are rapidly spreading worldwide and continue to be a global public health crisis. The use of repurposed drugs with the potential to inhibit SARS-CoV-2 could be a vital alternative approach when the novel therapeutic has not yet available. The guidelines for emergency treatment of COVID-19 vary across different countries and largely rely on the off-label prescription of repurposed drugs. As a result, clinical studies to generate robust efficacy data for these repurposed drugs are warranted to effectively fight against the ongoing COVID-19 pandemic.
The broad spectrum antiparasitic drug ivermectin has previously been shown to exhibit broad antiviral activities against many RNA and DNA viruses. It has a reliable safety profile with comprehensive data for decades especially in mass drug administration programs for river blindness prophylaxis in several countries in Africa. Owing to its strong inhibitory activity against the replication of SARS-CoV-2 in vitro and its putative role in reducing cytokine storm, the drug has been repurposed to treat COVID-19 patients and has shown promising results in several clinical studies. Ivermectin has thus gained a considerable attention as a potential treatment for COVID-19. However, the National Institute of Health (NIH) and World Health Organization (WHO) currently state that studies on using ivermectin to treat COVID-19 patients remain inconclusive due to insufficient data. Therefore, a large well designed randomized, double blinded, placebo-controlled trial to assess the efficacy of ivermectin is urgently needed.
Another important treatment option for COVID-19 is favipiravir, an antiviral drug for influenza treatment. Although the drug has not been approved for a COVID-19 treatment by the US-FDA, it has been included in Guidelines on clinical practice, diagnosis, treatment, and prevention of healthcare-associated infection for COVID-19 in Thailand. Favipiravir, a known inhibitor of RNA-dependent RNA polymerase, was shown to have an in vitro activity against SARS-CoV-2. The meta-analysis showed a significant improvement in clinical outcome at day 14 along with chest imaging in the favipiravir group compared to standard care. However, there are no significant differences in terms of clinical deterioration rates, viral clearance, oxygen support requirement and side effect profiles. There are still ongoing clinical trials assessing the effectiveness of favipiravir in the treatment of COVID-19.
Antivirals can be generally divided into direct-acting antivirals (DAA) and host-targeting drugs. For example, the widely used drug remdesivir repurposed to treat COVID-19 is a DAA, and chloroquine is considered a host-targeting drug. Because these repurposed drugs were not specifically designed and developed for COVID-19, they are likely to be less efficacious, and partner drugs need to be further explored. Finding a right combination for DAA is a common practice for developing virus treatment regimens. Relying on different modes of action and absence of unfavorable drug interaction, the combinations are usually additive or synergistic. It is important to note that our in vitro data demonstrated the synergistic profile for the combination of favipiravir and ivermectin against SARS-CoV-2. It resulted in 4-fold reduction in the half maximal inhibitory concentration (IC50) as compared to individual drugs, from 1.2 µM to 0.3 µM with a peak Loewe synergy score of over 33.2 and a mean score of 18.8 (noted that Loewe synergy score > 10 indicates synergistic effect).
In response to this COVID-19 pandemic crisis, especially in a resource limited setting like Thailand, clinical studies to evaluate affordable and implementable interventions are a priority and are urgently needed. Ivermectin, a cheap and safe drug, has been widely used in humans for decades, and it has also demonstrated an inhibitory effect against SARS-CoV-2 in vitro. Here, we aim to conduct a multi-center, double-blind, randomized controlled trial in Thailand to reveal the effectiveness of ivermectin as a combination therapy with favipiravir (standard treatment) for COVID-19. The results of this study will provide much needed information for pursuing larger efficacy clinical trials to confirm whether the combination could be effectively used to treat COVID-19. Also, they could provide information on the rate of viral clearance, the primary endpoint of this study, which was proposed to be a predictive surrogate of clinical benefits and used as a proper endpoint in the phase II trials for candidate drug screening for COVID-19.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Favipiravir plus Ivermectin | Experimental | Drug: Ivermectin TabletsIvermectin 600 mcg/kg once daily for 5 days in combination with Favipiravir for 5-10 days (1,800 mg twice a day in day 1 then 800 mg twice a day for the other days. For BW > 90 kg: 2,400 mg twice a day in day 1 then 1,000 mg twice a day for the other days). |
| Favipiravir plus Placebo | Placebo comparator | Other: PlaceboMatching placebo once daily for 5 days in combination with Favipiravir for 5-10 days (1,800 mg twice a day in day 1 then 800 mg twice a day for the other days. For BW > 90 kg: 2,400 mg twice a day in day 1 then 1,000 mg twice a day for the other days). |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Adult patient age between 18-65 years old
- Has confirmed SARS-CoV-2 infection by RT-PCR method using sample collected from nasopharyngeal swab (NP) and oropharyngeal swab (OP) with Ct value in either one of the following cases
- Has been admitted for medical care at the investigational sites
- In case of symptomatic patient, date of symptoms onset is ≤ 7 days prior to randomization. In case of asymptomatic patient, the first date of positive result from RT-PCR or antigen test kit for SARS-CoV-2 is ≤ 7 days prior to randomization.
- Qualified for the criteria to receive favipiravir for COVID-19 treatment according to Guidelines on clinical practice, diagnosis, treatment, and prevention of healthcare-associated infection for COVID-19 in Thailand in either one of the following cases
Key exclusion criteria (12 listed)
- Has severe or critical COVID-19 as defined in section 7.2.2.
- Bedridden (totally confined to bed)
- Has elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) over 3 times the upper range of normal limits, or history of liver cirrhosis
- Females only: Currently pregnant, as determined by positive β-human choriogonadotropin (HCG) test in urine, or breast-feeding
- Receiving other potential drugs for COVID-19 treatment prior to randomization including Remdesivir, Nitazoxanide, Chloroquine, Hydroxychloroquine, Azithromycin, Lopinavir-ritonavir, Famotidine, Tocilizumab, Baricitinib (except favipiravir)
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 Tablets6 mg/tablet | Drug | Favipiravir plus Ivermectin |
| PlaceboThe placebo has same form as Ivermectin. | Other | Favipiravir plus Placebo |
Primary outcome
The rate of SARS-CoV-2 viral clearance
Time frame: Day 1- Day 6
The rate of viral clearance as measured by Ct values from NP and OP swab once daily
5 secondary outcomes
Mortality rate
Time frame: Day 14 and Day 28
Progression to severe disease
Time frame: Day 1 to discharge Day, Day 14, Day 28
Duration of admission
Time frame: Day 1 to discharge Day
Oxygen requirement
Time frame: Day 1 to Day 28
Proportions of SARS-CoV-2 viral clearance
Time frame: Day 6
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2022.
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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.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ivermectin Tablets in people with COVID-19, run by Mahidol University at 2 sites in Thailand.
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 12 inclusion and 12 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 8 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Thailand. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The rate of SARS-CoV-2 viral clearance (time frame: Day 1- Day 6). 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 8 Jun 2022; AzTrials last refreshed its copy on 8 Nov 2026.