Clinical trial NCT04477083: Development and Validation of "Ready-to-Use" Inhalable Forms of Hydroxychloroquine for Treatment of COVID-19
Official title: Development and Validation of "Ready-to-Use" Inhalable Forms of Hydroxychloroquine for Treatment of COVID-19
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Covid19
Hydroxychloroquine Adverse Reaction
Keywords: Covid19
Hydroxychloroquine
Lead sponsor: Mansoura University
Sponsor class: OTHER
First posted: 2020-07-20
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: The first 20 consecutive patients (group A) will be treated by oral antibiotics, supportive treatment and inhalable hydroxychloroquine (HCQ). (In day 1, an inhaled hydroxychloroquine sulfate dose of 12 mg will be taken via nebulization three times/day (TID) as a loading dose. Then, starting from day 2, same dose of 12 mg of inhaled hydroxychloroquine will be taken twice/day (BID) as maintenance dose for 5 days. The subsequent 20 consecutive patients (group B) will receive the same treatment of group A but without inhalable hydroxychloroquine (HCQ). At day 7, all patients of both groups will be evaluated by clinical, laboratory and chest CT parameters. Patients of group B who still show no clinical, laboratory or radiological improvement will continue treatment by adding inhalable hydroxychloroquine (HCQ). for another 7 days and re-evaluated at day 14. Patients of group A who still show no significant improvement at day 7 only will be re-checked at day 14.
Primary purpose: TREATMENT

Brief summary: In this project, we aimed at developing new "Ready-to-Use" inhalable forms of HCQ that can be used directly through nebulization or using dry powder inhalers (DPIs). These inhaled forms would allow a simple and direct delivery of the drug (HCQ) specifically towards the throat and the lung which are the main sites for the COVID-19 viral infection. Hence, the drug can be available at higher concentrations in the throat and lungs as compared with the currently used treatment protocols, while minimizing the drug systemic concentrations and its presence in other body organs, and thus enhancing the drug efficacy with significantly limiting its side effects. Besides, using inhalable forms can be more convenient to patients suffering from gastrointestinal complications from the disease that can limit the absorption of oral forms. Moreover, the proposed inhalable forms are designed in such a way to hide the drug from the immune system (confer stealth characteristics) using FDA-approved excipients to minimize/avoid any immune response towards the drug as was noted towards it in its oral form that's used in the treatment protocol of COVID-19. In addition, the inhaled formulations will be designed to maintain the overall simplicity and scalability of the preparation which is critical during this urgent pandemic situation. The cost of the final formulation is also taken into consideration since the drug is intended for treatment of thousands or probably millions of patients around the world including countries with limited economic capabilities.


Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 year
* Laboratory (RT-PCR) positive of SARS-COV-2 (Moderate cases)
* Chest CT with pneumonia.
* SaO2/SPO2 ratio \> 93% or PaO2/FIO2 ratio \> 300 mmHg under the condition in the hospital room.
* Welling to participate and able to give fully informed consent

Exclusion Criteria:

* Severe and critical illness.
* Retinopathy and other retinal diseases.
* Arrhythmias.
* QT ≥ 400 msec
* Receiving cardiac drugs
* Severe liver disease.
* Pregnancy or lactation.
* Previous treatment of COVID-19.

Primary outcomes:
measure: Time to clinical recovery defined as 3 days afebrile with improved cough and other clinical signs
timeFrame: 15 days
measure: Time to achieve viral clearance state determined by two successive negative PCR results for two oropharyngeal swabs separated by 48 hours.
timeFrame: 15 days
Secondary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: 15 days
Other outcomes:
Locations:
city: Mansoura
country: Egypt
facility: Mansoura University Hospital
state: Outside U.S./Canada
Study officials:
References: