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Isotretinoin in Treatment of COVID-19 (Randomized)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04361422
Recruitment Status : Not yet recruiting
First Posted : April 24, 2020
Last Update Posted : April 24, 2020
Sponsor:
Information provided by (Responsible Party):
Lamia Elgarhy, Tanta University

Tracking Information
First Submitted Date  ICMJE April 21, 2020
First Posted Date  ICMJE April 24, 2020
Last Update Posted Date April 24, 2020
Estimated Study Start Date  ICMJE April 21, 2020
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 22, 2020)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures
 (submitted: April 22, 2020)
Laboratory clearance [ Time Frame: 14-30 day ]
  1. Proportion of patients with negative COVID-19 PCR test at day 30 in per protocol population as per throat swab
  2. Change in COVID-19 virus load from baseline to day 30
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Isotretinoin in Treatment of COVID-19
Official Title  ICMJE Evaluation of the Safety and Efficacy of Isotretinoin in Treatment of COVID-19: Clinical Study
Brief Summary 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE COVID-19
Intervention  ICMJE Drug: 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.
Other Name: standard COVID-19 therapy
Study Arms  ICMJE
  • Active Comparator: Isotretinoin
    13 cis retinoic acid 0.5 mg/kg/day in 2 divided doses orally for one month
    Intervention: Drug: Isotretinoin Only Product in Oral Dose Form
  • Sham Comparator: 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
    Intervention: Drug: Isotretinoin Only Product in Oral Dose Form
  • Active Comparator: 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.
    Intervention: Drug: Isotretinoin Only Product in Oral Dose Form
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: April 22, 2020)
300
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2020
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 40 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04361422
Other Study ID Numbers  ICMJE 9469305c
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Lamia Elgarhy, Tanta University
Study Sponsor  ICMJE Tanta University
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Tanta University
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP