Isotretinoin in Treatment of COVID-19

NCT ID: NCT04361422

Last Updated: 2020-09-23

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-01
• Study Completion Date: 2021-12-31

Brief 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.

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:

1. Hypercholesterolemia

2. Hypertriglyceridemia

3. Liver disease

4. Renal disease

5. Sjögren syndrome

6. Pregnancy

7. Lactation

8. Depressive disorder

9. Contraindications for hormonal contraception or intrauterine device.

Conditions

COVID-19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Isotretinoin

13 cis retinoic acid 0.5 mg/kg/day in 2 divided doses orally for one month

Group Type: ACTIVE_COMPARATOR

Isotretinoin Only Product in Oral Dose Form

Intervention Type: DRUG

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.

Standard COVID-19 therapy

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 Type: SHAM_COMPARATOR

Isotretinoin Only Product in Oral Dose Form

Intervention Type: DRUG

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.

Standard COVID-19 therapy+ isotretinoin

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.

Group Type: ACTIVE_COMPARATOR

Isotretinoin Only Product in Oral Dose Form

Intervention Type: DRUG

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.

Interventions

Isotretinoin Only Product in Oral Dose Form

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.

Intervention Type: DRUG

Other Intervention Names

standard COVID-19 therapy

Eligibility Criteria

Inclusion Criteria

• Clinical and laboratory diagnosis of COVID-19.
• Age range 18-40

Exclusion Criteria

1. Hypercholesterolemia

2. Hypertriglyceridemia

3. Liver disease

4. Renal disease

5. Sjögren syndrome

6. Pregnancy

7. Lactation

8. Depressive disorder

9. Contraindications for hormonal contraception or intrauterine device.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tanta University

OTHER

Sponsor Role: lead

Responsible Party

Lamia Elgarhy

Associate professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

Lamia H Elgarhy

Role: CONTACT

lamia_elgarhy@yahoo.com

+201069469305

Other Identifiers

9469305c

Identifier Type: -

Identifier Source: org_study_id