Use of a Combined Regimen of Fluoxetine, Prednisolone and Ivermectin in the Treatment of Mild COVID-19 to Prevent Disease Progression Progression in Papua New Guinea

• Status: Not yet recruiting
• Trial end date: 2022-07-30
• Target enrollment: 0
• Participant gender: All

Summary

The Fluo-Pred-Iver clinical trial will test the efficacy of a combined regimen of Fluoxetine, Prednisolone and Ivermectin (Fluo-Pred-Iver), as treatment for ambulatory patients with mild COVID-19. The overarching idea of the work proposed herein is to investigate the use of Fluo-Pred-Iver to treat COVID-19, conducting a randomized controlled clinical trial to evaluate a new indication for these widely available drugs. It is estimated to include 954 participants.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Oriol Mitja
• Collaborators: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia; National Department of Health, Papua New Guinea
• Treatments: Albendazole; Ascorbic Acid; Fluoxetine; Ivermectin; Prednisolone

Criteria

Inclusion Criteria:

1. Adult male or female individuals of ≥18 years old.

2. In women of childbearing potential, negative pregnancy test at inclusion/baseline visit.

3. Has confirmed SARS-CoV-2 infection as determined by PCR, a validated NAAT (i.e., GeneXpert), or validated antigen rapid diagnostic test from nasopharyngeal swabs ≤5 days prior to inclusion/baseline visit.

4. Symptomatic with mild COVID-19 with symptoms onset date ≤ 7 days prior to inclusion/baseline visit. Mild COVID-19, as defined per NIH: Individuals who have any of the common signs and/or symptoms of COVID-19 (i.e., fever, cough, sore throat, malaise, headache, muscle pain) without shortness of breath, dyspnoea, or abnormal chest imaging.

5. Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study.

6. Has understood the information provided and capable of giving informed consent.

Exclusion Criteria:

1. If female, pregnant or breastfeeding, or planning a pregnancy during the study.

2. Moderate COVID-19, as defined per NIH:

a. Moderate COVID-19: Individuals who have evidence of lower respiratory disease by clinical assessment or imaging and a saturation of oxygen (SpO2) ≥94% on room air at sea level.

3. Severe or critical COVID-19, as defined per NIH:

1. Severe COVID-19: respiratory frequency >30 breaths per minute, SpO2 <94% on room air at sea level, ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) <300 mmHg, or lung infiltrates >50%.

2. Critical COVID-19: respiratory failure, septic shock, and/or multiple organ dysfunction.

4. History of previous confirmed SARS-CoV-2 infection.

5. History of significantly abnormal liver function (Child Pugh C).

6. History of chronic kidney disease (CKD) ≥ stage 4 or need of dialysis treatment.

7. Any pre-existing condition that increases risk of thrombosis.

8. History of allergic reactions to ivermectin, fluoxetine, prednisolone, or vitamins C, albendazole, any of its excipients.

9. Concomitant use of medications that are highly dependent of CYP 2D6 for clearance and for which elevated plasma concentrations may be associated with serious and/or life-threatening events.

1. Phenytoin

2. Tricyclic antidepressants

3. Antipsychotics: phenothiazines (i.e., chlorpromazine) haloperidol and most atypical (i.e., amitriptyline, aripiprazole, brexpiprazole, risperidone).

4. Donepezil

5. Tamoxifen

6. Antiarrhytmics: propafenone, flecainide

7. Amphetamine

10. Concomitant use of SSRIs, SNRIs, or tricyclic antidepressants, linezolid, or methylene blue (rationale: increased risk of serotonin syndrome or TCA overdose).

11. Concomitant use of drugs that could prolong the QT interval:

1. Specific antipsychotics: ziprasidone, iloperidone, chlorpromazine, mesoridazine, droperidol

2. Specific antibiotics: erythromycin, gatifloxacin, moxifloxacin, sparfloxacin

3. Class 1A antiarrhytmics: amiodarone, sotalol

12. Concomitant use of donepezil (S1R agonist) or sertraline (S1R antagonist)

13. Uncontrolled psychiatric disorders, or suicidal ideation.

14. Inability to consent and/or comply with study protocol, in the opinion of the investigator.