Status:
UNKNOWN
Assessment the Activity Value of Isotretinoin (13- Cis-Retinoic Acid ) in the Treatment of COVID-19 ( Isotretinoin in Treatment of COVID-19) (Randomized)
Lead Sponsor:
Kafrelsheikh University
Collaborating Sponsors:
The First Hospital of Jilin University
2-Montefiore Health System and Albert Einstein College of Medicine, Newyork, United States of America (U.S.A).
Conditions:
COVID19
Eligibility:
All Genders
18-80 years
Phase:
PHASE3
Brief Summary
Assessment the Activity Value of Isotretinoin (13- Cis-Retinoic Acid ) in the Treatment of COVID-19 Mahmoud ELkazzaz(1),Tamer Haydara(2), Mohamed Abdelaal(3), Abedelaziz Elsayed(4) ,Yousry Abo-amer(5...
Detailed Description
The study is a randomized interventional comparative Phase III trial. 10000 adult male and female patients with positive COVID-19 diagnosis and fulfilling the below outlined inclusion criteria will be...
Eligibility Criteria
Inclusion
- Adult SARI patients with 2019-ncov infection confirmed by PCR; Absolute value of lymphocytes \< 0. 6x 109/L; Severe respiratory failure within 48 hours and requires admission to ICU. (severe respiratory failure was defined as PaO2/FiO2 \< 200 mmHg and was supported by positive pressure mechanical ventilation (including non-invasive and invasive mechanical ventilation, PEEP\>=5cmH2O))
Exclusion
- Age \< 18 Pregnant Allergic to experimental drugs and patients have the following conditions:
- Hypercholesterolemia
- Hypertriglyceridemia
- Liver disease
- Renal disease
- Sjögren syndrome
- Pregnancy
- Lactation
- Depressive disorder
- Body mass index less than 18 points or higher than 25 points
- Contraindications for hormonal contraception or intrauterine device.
- Autoimmune diseases A history of organ, bone marrow or hematopoietic stem cell transplantation
- Patients receiving anti-hcv treatment
- Permanent blindness in one eye
- History of iritis, endophthalmitis, scleral inflammation or retinitis 15-90 days of retinal detachment or eye surgery
- 16-The competent physician considered it inappropriate to participate in the study
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- Safety and promising features of isotretinoin in tne era of COVID 2019 according Principal Investigator Protocol:
- This medication have the feature of Aerosolized Drug Delivery to increase its efficacy beside Oral administration, Which makes it distinct from other medication in which should dose be only given orally. A study demonstrated that treating with 13 cis retinoic acid aerosolized via inhalation rout did not cause any damage in lung cells.
- Repeated high doses of 13 cis retinoic by inhalation resulted in moderate loss of body weight, but microscopic investigation of ten tissues including lung and oesophagus did not detect any significant aerosol-induced damage. The results suggest that administration of isotretinoin via powder aerosol inhalation is probably superior to its application via the oral route in terms of achieving efficacious drug concentrations in the lung.
- Inhaled isotretinoin might provide sufficient drug to the target cells for efficacy while avoiding systemic toxicity.
- A study demonstrated that 13 cis retinoic is used in treating Emphysema (emphysema is a lung condition that causes shortness of breath)
- RA has been reported to induce formation of new alveoli and returns elastic recoil in the lung to approximately normal values in animal models of emphysema.
- Strong expectation of complete COVID -19 blockade from cell entry and infection depending on strong ethics, researches and references.
- Availability of our compounds.
- Ease of application.
- Expectation of COVID -19 treating by isotretinoin via more than one distinct mechanism.
- Expectation of High induction of anti- inflammatory T cells and significant inhibition of IL-6 at low concentrations of isotretinoin.
- Controlling Accompanying cytokine storm.
- No interactions with Egyptian protocol drugs were found.
- (13- cis -Retinoic acid ) can be given in the form of aerosol to avoid these systemic side effects. A clinical trial conducted on 148 subject from 5 university hospitals to evaluate the possibility of retinoids in the treatment of emphysema. The patients, were randomized to receive 13-cis retinoic acid (1 mg/kg/day, daily or ATRA at either low dose (1 mg/kg/day for 4 days/wk) or high dose (2 mg/kg/day for 4 days/wk), placebo for six months, followed by a three-month crossover phase. then, they were observed for an additional nine months before the final evaluation. In the trial, retinoids(13 cis retinoic acid ) were proven to be safe as the drug-related AEs were generally mild\[188\]. A study reported that the application of aerosolized RA system led to a rise of RA levels in lung, but not plasma. or liver. In lung concentration and levels of retinol, retinyl palmitate and retinyl stearate also showed to be unchanged \[189\] A study on rabbits demonstrated that 13 cis retinoic acid can be given in the form of aerosol without serious side effects In this study repeated elevated doses of 13 cis retinoic acid by inhalation caused moderate loss of body weight, but microscopic examination of ten tissues including oesophagus and lung did not found any significant inhalation-induced injury or damage therefore aerosolized 13 cis retinoic acid might provide sufficient therapy to the target cells in lung for efficacy while avoiding systemic toxicity © 2000 Cancer Research Campaign\[190\]
Key Trial Info
Start Date :
August 1 2021
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
November 1 2021
Estimated Enrollment :
100000 Patients enrolled
Trial Details
Trial ID
NCT04353180
Start Date
August 1 2021
End Date
November 1 2021
Last Update
August 5 2021
Active Locations (2)
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1
Faculty of Medicine, Kafr El-sheikh University
Cairo, Kafr el-Sheikh Governorate, Egypt, 33511
2
Faculty of Medicine, Kafr El-sheikh University
Cairo, Egypt