COVID-19Phase 3RandomizedNCT04361422
Isotretinoin in Treatment of COVID-19
A Phase 3 study testing Isotretinoin Only Product in Oral Dose Form in people with COVID-19, run by Tanta University.
Trial summary
Contributors: Lamia Elgarhy, Sabah El-Gaeish 1, Eman Hamed 2 , Wagdy Fathy2 Department of Dermatology, Department of Pharmacology1 , Faculty of Medicine, Tanta University, Department of Chest, Faculty of Medicine, Suez Canal University2. Read more about this study
- Who is it for?
- Ages 18 to 40 years
- Conditions the study is for
- COVID-19
- What is being tested?
- Isotretinoin Only Product in Oral Dose Form
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 300 participants
- Where
- No sites listed yet
- Study dates
- 1 Dec 2020to Dec 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 40 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Clinical and laboratory diagnosis of COVID-19.
- Age range 18-40
Who cannot join
- Hypercholesterolemia
- Hypertriglyceridemia
- Liver disease
- Renal disease
- Sjögren syndrome
- Pregnancy
Show all 9Show fewer
- Lactation
- Depressive disorder
- Contraindications for hormonal contraception or intrauterine device.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Evaluation of the Safety and Efficacy of Isotretinoin in Treatment of COVID-19: Clinical Study
Contributors:
Lamia Elgarhy, Sabah El-Gaeish 1, Eman Hamed 2 , Wagdy Fathy2 Department of Dermatology, Department of Pharmacology1 , Faculty of Medicine, Tanta University, Department of Chest, Faculty of Medicine, Suez Canal University2.
Read more
Abstract:
The COVID-19 pandemic caused by SARS-COV-2 has infected over 2,000,000 people causing over 150,000 deaths. A key host cellular protein required for the virus entry is angiotensin-converting enzyme 2 (ACE2) whose expression has been demonstrated in many tissues including alveolar epithelial type II cells in lungs, oral mucosa and intestine, heart, kidney, endothelium and skin. ACE2-expressing cells can act as home cells and are prone to SARS-CoV-2 infection as ACE2 receptor facilitates cellular viral entry and replication. (1) Fang et al. has suggested that patients with hypertension and diabetes mellitus may be at higher risk of SARS-CoV-2 infection, as these patients are often treated with ACE inhibitors (ACEIs) or angiotensin II type-I receptor blockers (ARBs), which have been previously suggested to increase ACE2 expression. (2) In another study by Sinha et al who analyzed a publicly available Connectivity Map (CMAP) dataset of pre/post transcriptomic profiles for drug treatment in cell lines for over 20,000 small molecules, isotretinoin was the strongest down-regulator of ACE 2 receptors. On the other hand, they found 6 drugs in CMAP that are currently being investigated in clinical trials for treating COVID-19 (chloroquine, thalidomide, methylprednisolone, losartan, lopinavir and ritonavir, from clinicaltrials.gov), none of which was found to significantly alter ACE2 expression (P>0.1) (3) Moreover, Wu et al, demonstrated that isotretinoin is a Potential papain like protease (PLpro) inhibitors which is a protein encoded by SARS-CoV-2 genes and considered one of the proteins that should be targeted in COVID-19 treatment by performing target-based virtual ligand screening. (4) In addition, isotretinoin was reported to increase CD4 counts and markedly decrease viremia in HIV positive patients suffering from acne vulgaris. (5) Currently, a study is running to evaluate the effect of isotretinoin on immune activation among HIV-1 infected subjects with incomplete CD4+ T cell recovery. (6) From this point, we can suggest that patient taking isotretinoin therapy may be immune against SARS-COV-2 and it can also have a therapeutic effect by prevention of further progression of the virus. Several potential mechanisms of action of Chloroquine/Hydroxychloroquine against SARS-CoV-2 have been postulated and they are actually used in treatment regimens for COVID-19.(7) It was reported that chloroquine increase the blood level of isotretinoin, so lower doses is required when combined. We assume to test the efficacy of isotretinoin in treatment of COVID-19 versus combined therapy with the standard treatment of COVID-19.
Read the detailed description
The study is a randomized interventional comparative Phase III trial. The duration of the trial for each subject is expected to be 3 months. The duration for each individual subject includes one-month study treatment and 3 months follow-up time. Recruitment of subjects will start in April 2020.
150 adult male and female patients with positive COVID-19 diagnosis and fulfilling the below outlined inclusion criteria will be enrolled into the study. Trial population will consist of both genders.
Name of tested drug: Isotretinoin. All consenting adult patients having confirmed COVID-19 will be recruited and randomly and blindly allocated in a 1:1:1 ratio to the following arms:
Group (1): 50 patients will receive isotretinoin 0.5 mg/kg/day for one month or until viral clearance.
Group (2): 50 patients will receive standard therapy for COVID-19 (Paracetamol 500 mg /6h, Hydroxychloroquine 500 mg/ 12h, Oseltamivir 150 mg /12 h for 5 days, Azithromycin 1 gm first day then 500 mg/day for 1st line or Clarithromycin 500 mg/12 h for 7-14 days, Ascorbic acid 500 mg/12 h and Cyanocobalamin IV once daily plus Lopinavir 400mg/Ritonavir 100 mg caps 2 capsules twice daily in severe cases).
Group (3): 50 patients will receive standard therapy for COVID-19 + isotretinoin 0.25 mg/kg/day for one month or until viral clearance.
Inclusion Criteria:
- Clinical and laboratory diagnosis of COVID-19.
- Age range 18-40
Exclusion Criteria:
- Have the following conditions:
- Hypercholesterolemia
- Hypertriglyceridemia
- Liver disease
- Renal disease
- Sjögren syndrome
- Pregnancy
- Lactation
- Depressive disorder
- Contraindications for hormonal contraception or intrauterine device.
- Conditions
- COVID-19
- Being tested
- Isotretinoin Only Product in Oral Dose Form
- Keywords
- Isotretinoin, COVID-19
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Isotretinoin Only Product in Oral Dose FormDrug
Also called standard COVID-19 therapy
assess antiviral efficacy, tolerability and safety of oral isotretinoin in the treatment of COVID-19 versus combined oral isotretinoin with standard therapy for COVID-19 versus the standard therapy alone.
| Study group | Role | What they receive |
|---|---|---|
| Isotretinoin | Active comparator | 13 cis retinoic acid 0.5 mg/kg/day in 2 divided doses orally for one month Receives: Drug: Isotretinoin Only Product in Oral Dose Form |
| Standard COVID-19 therapy | Sham comparator | Paracetamol 500 mg /6h, Hydroxychloroquine 500 mg/ 12h, Oseltamivir 150 mg /12 h for 5 days, Azithromycin 1 gm first day then 500 mg/day for 1st line or Clarithromycin 500 mg/12 h for 7-14 days, Ascorbic acid 500 mg/12 h and Cyanocobalamin IV once daily plus Lopinavir 400mg/Ritonavir 100 mg caps 2 capsules twice daily in severe cases Receives: Drug: Isotretinoin Only Product in Oral Dose Form |
| Standard COVID-19 therapy+ isotretinoin | Active comparator | Paracetamol 500 mg /6h, Hydroxychloroquine 500 mg/ 12h, Oseltamivir 150 mg /12 h for 5 days, Azithromycin 1 gm first day then 500 mg/day for 1st line or Clarithromycin 500 mg/12 h for 7-14 days, Ascorbic acid 500 mg/12 h and Cyanocobalamin IV once daily plus Lopinavir 400mg/Ritonavir 100 mg caps 2 capsules twice daily in severe cases) plus 13 cis retinoic acid 0.5 mg/kg/day in 2 divided doses orally forone month. Receives: Drug: Isotretinoin Only Product in Oral Dose Form |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical clearance
- Difference in time to resolution of clinical signs and symptoms of COVID-19 treated with isotretinoin, standard therapy or combined therapy as assessed by daily assessment
Measured: 14-30 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2020
- Study start1 Dec 2020 (estimated)
- Primary completionAug 2021 (estimated)
- Study completionDec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies of the same condition, open and under way.
- More trials run by Tanta 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tanta University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lamia Elgarhy, Tanta University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04361422
- Sponsor's protocol ID
- 9469305c
- Acronym
- Randomized
- Status last verified
- Sep 2020
- First submitted
- 21 Apr 2020
- Last updated
- 23 Sep 2020
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Elgarhy LH, El-Ghaiesh SH, Hamed E, Abdelfatah W. Evaluation of the safety and efficacy of isotretinoin in treatment of COVID-19 : A randomized controlled clinical trial. Contemp Clin Trials. 2025 Mar;150:107813. doi: 10.1016/j.cct.2025.107813. Epub 2025 Jan 16.
PubMed 39826827
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Safety and Efficacy of Isotretinoin in Treatment of COVID-19: Clinical Study
- ClinicalTrials.gov ID
- NCT04361422
- Acronym / sponsor ID
- Randomized / 9469305c
- Conditions
- COVID-19
- Keywords
- Isotretinoin, COVID-19
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Tanta UniversityUniversity, hospital or other
- Study start
- 1 Dec 2020 (estimated)
- Primary completion
- Aug 2021 (estimated)
- Study completion
- Dec 2021 (estimated)
- First posted
- 24 Apr 2020 (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.
Contributors:
Lamia Elgarhy, Sabah El-Gaeish 1, Eman Hamed 2 , Wagdy Fathy2 Department of Dermatology, Department of Pharmacology1 , Faculty of Medicine, Tanta University, Department of Chest, Faculty of Medicine, Suez Canal University2.
Abstract:
The COVID-19 pandemic caused by SARS-COV-2 has infected over 2,000,000 people causing over 150,000 deaths. A key host cellular protein required for the virus entry is angiotensin-converting enzyme 2 (ACE2) whose expression has been demonstrated in many tissues including alveolar epithelial type II cells in lungs, oral mucosa and intestine, heart, kidney, endothelium and skin. ACE2-expressing cells can act as home cells and are prone to SARS-CoV-2 infection as ACE2 receptor facilitates cellular viral entry and replication. (1) Fang et al. has suggested that patients with hypertension and diabetes mellitus may be at higher risk of SARS-CoV-2 infection, as these patients are often treated with ACE inhibitors (ACEIs) or angiotensin II type-I receptor blockers (ARBs), which have been previously suggested to increase ACE2 expression. (2) In another study by Sinha et al who analyzed a publicly available Connectivity Map (CMAP) dataset of pre/post transcriptomic profiles for drug treatment in cell lines for over 20,000 small molecules, isotretinoin was the strongest down-regulator of ACE 2 receptors. On the other hand, they found 6 drugs in CMAP that are currently being investigated in clinical trials for treating COVID-19 (chloroquine, thalidomide, methylprednisolone, losartan, lopinavir and ritonavir, from clinicaltrials.gov), none of which was found to significantly alter ACE2 expression (P>0.1) (3) Moreover, Wu et al, demonstrated that isotretinoin is a Potential papain like protease (PLpro) inhibitors which is a protein encoded by SARS-CoV-2 genes and considered one of the proteins that should be targeted in COVID-19 treatment by performing target-based virtual ligand screening. (4) In addition, isotretinoin was reported to increase CD4 counts and markedly decrease viremia in HIV positive patients suffering from acne vulgaris. (5) Currently, a study is running to evaluate the effect of isotretinoin on immune activation among HIV-1 infected subjects with incomplete CD4+ T cell recovery. (6) From this point, we can suggest that patient taking isotretinoin therapy may be immune against SARS-COV-2 and it can also have a therapeutic effect by prevention of further progression of the virus. Several potential mechanisms of action of Chloroquine/Hydroxychloroquine against SARS-CoV-2 have been postulated and they are actually used in treatment regimens for COVID-19.(7) It was reported that chloroquine increase the blood level of isotretinoin, so lower doses is required when combined. We assume to test the efficacy of isotretinoin in treatment of COVID-19 versus combined therapy with the standard treatment of COVID-19.
Detailed description
The study is a randomized interventional comparative Phase III trial. The duration of the trial for each subject is expected to be 3 months. The duration for each individual subject includes one-month study treatment and 3 months follow-up time. Recruitment of subjects will start in April 2020.
150 adult male and female patients with positive COVID-19 diagnosis and fulfilling the below outlined inclusion criteria will be enrolled into the study. Trial population will consist of both genders.
Name of tested drug: Isotretinoin. All consenting adult patients having confirmed COVID-19 will be recruited and randomly and blindly allocated in a 1:1:1 ratio to the following arms:
Group (1): 50 patients will receive isotretinoin 0.5 mg/kg/day for one month or until viral clearance.
Group (2): 50 patients will receive standard therapy for COVID-19 (Paracetamol 500 mg /6h, Hydroxychloroquine 500 mg/ 12h, Oseltamivir 150 mg /12 h for 5 days, Azithromycin 1 gm first day then 500 mg/day for 1st line or Clarithromycin 500 mg/12 h for 7-14 days, Ascorbic acid 500 mg/12 h and Cyanocobalamin IV once daily plus Lopinavir 400mg/Ritonavir 100 mg caps 2 capsules twice daily in severe cases).
Group (3): 50 patients will receive standard therapy for COVID-19 + isotretinoin 0.25 mg/kg/day for one month or until viral clearance.
Inclusion Criteria:
- Clinical and laboratory diagnosis of COVID-19.
- Age range 18-40
Exclusion Criteria:
- Have the following conditions:
- Hypercholesterolemia
- Hypertriglyceridemia
- Liver disease
- Renal disease
- Sjögren syndrome
- Pregnancy
- Lactation
- Depressive disorder
- Contraindications for hormonal contraception or intrauterine device.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Isotretinoin | Active comparator | Drug: Isotretinoin Only Product in Oral Dose Form13 cis retinoic acid 0.5 mg/kg/day in 2 divided doses orally for one month |
| Standard COVID-19 therapy | Sham comparator | Drug: Isotretinoin Only Product in Oral Dose FormParacetamol 500 mg /6h, Hydroxychloroquine 500 mg/ 12h, Oseltamivir 150 mg /12 h for 5 days, Azithromycin 1 gm first day then 500 mg/day for 1st line or Clarithromycin 500 mg/12 h for 7-14 days, Ascorbic acid 500 mg/12 h and Cyanocobalamin IV once daily plus Lopinavir 400mg/Ritonavir 100 mg caps 2 capsules twice daily in severe cases |
| Standard COVID-19 therapy+ isotretinoin | Active comparator | Drug: Isotretinoin Only Product in Oral Dose FormParacetamol 500 mg /6h, Hydroxychloroquine 500 mg/ 12h, Oseltamivir 150 mg /12 h for 5 days, Azithromycin 1 gm first day then 500 mg/day for 1st line or Clarithromycin 500 mg/12 h for 7-14 days, Ascorbic acid 500 mg/12 h and Cyanocobalamin IV once daily plus Lopinavir 400mg/Ritonavir 100 mg caps 2 capsules twice daily in severe cases) plus 13 cis retinoic acid 0.5 mg/kg/day in 2 divided doses orally forone month. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Clinical and laboratory diagnosis of COVID-19.
- Age range 18-40
Key exclusion criteria (9 listed)
- Hypercholesterolemia
- Hypertriglyceridemia
- Liver disease
- Renal disease
- Sjögren syndrome
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 |
|---|---|---|
| Isotretinoin Only Product in Oral Dose FormAlso: standard COVID-19 therapyassess antiviral efficacy, tolerability and safety of oral isotretinoin in the treatment of COVID-19 versus combined oral isotretinoin with standard therapy for COVID-19 versus the standard therapy alone. | Drug | Isotretinoin, Standard COVID-19 therapy, Standard COVID-19 therapy+ isotretinoin |
Primary outcome
Clinical clearance
Time frame: 14-30 day
1. Difference in time to resolution of clinical signs and symptoms of COVID-19 treated with isotretinoin, standard therapy or combined therapy as assessed by daily assessment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2020.
- Derived from this study: PubMed 39826827Elgarhy LH, El-Ghaiesh SH, Hamed E, Abdelfatah W. Evaluation of the safety and efficacy of isotretinoin in treatment of COVID-19 : A randomized controlled clinical trial. Contemp Clin Trials. 2025 Mar;150:107813. doi: 10.1016/j.cct.2025.107813. Epub 2025 Jan 16.
- 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.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Isotretinoin Only Product in Oral Dose Form in people with COVID-19, run by Tanta University.
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 2 inclusion and 9 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 23 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
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 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 Lamia H Elgarhy (+201069469305, lamia_elgarhy@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical clearance (time frame: 14-30 day). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04361422, which also lists 1 linked publication.
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 23 Sep 2020.