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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

Primary Purpose

SARS-CoV2 Infection, COVID-19

Status

Withdrawn

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

Combination regimen: Fluoxetine, Prednisolone, Ivermectin

Combination regimen: Albendazole, Vitamin C

About this trial

This is an interventional treatment trial for SARS-CoV2 Infection focused on measuring Ivermectin, Fluoxetin, Prednisolone

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Adult male or female individuals of ≥18 years old.
In women of childbearing potential, negative pregnancy test at inclusion/baseline visit.
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.
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.
Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study.
Has understood the information provided and capable of giving informed consent.

Exclusion Criteria:

If female, pregnant or breastfeeding, or planning a pregnancy during the study.
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.
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.
History of previous confirmed SARS-CoV-2 infection.
History of significantly abnormal liver function (Child Pugh C).
History of chronic kidney disease (CKD) ≥ stage 4 or need of dialysis treatment.
Any pre-existing condition that increases risk of thrombosis.
History of allergic reactions to ivermectin, fluoxetine, prednisolone, or vitamins C, albendazole, any of its excipients.
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
Concomitant use of SSRIs, SNRIs, or tricyclic antidepressants, linezolid, or methylene blue (rationale: increased risk of serotonin syndrome or TCA overdose).
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
Concomitant use of donepezil (S1R agonist) or sertraline (S1R antagonist)
Uncontrolled psychiatric disorders, or suicidal ideation.
Inability to consent and/or comply with study protocol, in the opinion of the investigator.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

Combined Regime of Fluoxetine, Prednisolone and Ivermectin

Combination of Vitamin C and Albendazole

Arm Description

Fluoxetine: 20mg tablet; 20 mg; once daily for 10 days; oral Prednisolone: 25 mg tablet; 25mg; once daily for 5 days; oral Ivermectin: 3 mg tablet; 0.4 mg/kg; once daily for 5 days; oral

Vitamin C: 50 mg tablet; 1 tablet; Once daily for 10 days; Oral Albendazole; 200 mg; 1 tablet; Once daily for 5 days; Oral Vitamin C: 50 mg tablet; 0.13 tablet/kg*; Once daily for 5 days; Oral *Same number of tablets than for Ivermectin

Outcomes

Primary Outcome Measures

COVID-19 disease progression

This is a composite endpoint of moderate, severe or critical COVID-19 and Emergency Room attendace or hospitalization, or death

SARS-CoV-2 viral load

Reduction in SARS-CoV-2 viral load in nasopharyngeal swabs at day 7 after start of treatment, as determined by RT-qPCR

Secondary Outcome Measures

COVID-19 WHO Clinical progression scale score

Change in COVID-19 WHO Clinical progression scale score

Adverse Events

Incidence of Adverse Events

Full Information

NCT ID

NCT05283954

First Posted

March 16, 2022

Last Updated

March 7, 2023

Sponsor

Oriol Mitja

Collaborators

National Department of Health, Papua New Guinea, Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia

1. Study Identification

Unique Protocol Identification Number

NCT05283954

Brief Title

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

Official Title

Use of a Combined Regimen of Fluoxetine, Prednisolone and Ivermectin in the Treatment of Mild COVID-19 to Prevent Disease Progression in Papua New Guinea: a Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Withdrawn

Why Stopped

Lack of funding

Study Start Date

May 1, 2022 (Anticipated)

Primary Completion Date

June 30, 2022 (Anticipated)

Study Completion Date

July 30, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Oriol Mitja

Collaborators

National Department of Health, Papua New Guinea, Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

Brief 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.

Detailed Description

In this study, individuals who have a confirmed SARS-CoV-2 infection, as determined by a PCR or antigen rapid diagnostic test within the last 5 days, will be informed about the study. Interested participants will be screened for eligibility criteria by research study staff. After review of inclusion and exclusion criteria, informed consent will be obtained. Participants who consent will be randomized to receive a combined regimen of Fluoxetine, Prednisolone and Ivermectin (Fluo-Pred-Iver), or a combined regimen of Albendazole and Vitamin C as control. Patients will be followed remotely and/or in persona with visits on day 3, 7, 10 and 14 after inclusion. The primary objective will be to measure the proportion of a composite endpoint of moderate, severe or critical COVID-19 (as defined by NIH) and Emergency Department attendance of hospitalization, or death up to day 14. The reduction of SARS-CoV-2 viral load at day 7 measured by RT-qPCR will also be evaluated. As secondary endpoints, the therapeutic potential of early administration of the combined regimen Fluo-Pred-Iver in reducing WHO Clinical progression scale score and the safety and tolerability of Fluo-Pred-Iver will be evaluated.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

SARS-CoV2 Infection, COVID-19

Keywords

Ivermectin, Fluoxetin, Prednisolone

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare Provider

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Combined Regime of Fluoxetine, Prednisolone and Ivermectin

Arm Type

Experimental

Arm Description

Fluoxetine: 20mg tablet; 20 mg; once daily for 10 days; oral Prednisolone: 25 mg tablet; 25mg; once daily for 5 days; oral Ivermectin: 3 mg tablet; 0.4 mg/kg; once daily for 5 days; oral

Arm Title

Combination of Vitamin C and Albendazole

Arm Type

Other

Arm Description

Intervention Type

Drug

Intervention Name(s)

Combination regimen: Fluoxetine, Prednisolone, Ivermectin

Intervention Description

Subjects will receive the following treatments: Fluoxetine 20 mg oral tablets: One tablet right after randomization (Day 0) followed by one daily tablet for the following 09 days. Prednisolone 25 mg oral tablets: One tablet right after randomization (Day 0) followed by one daily tablet for the following 04 days. Ivermectin 3 mg oral tablets: Tablets started right after randomization (Day 0; 400mcg/ kg dosing), administered once a day for 05 consecutive days.

Intervention Type

Drug

Intervention Name(s)

Combination regimen: Albendazole, Vitamin C

Intervention Description

Subjects will receive the following treatments: Vitamin C 50 mg oral tablets: One tablet right after randomization (Day 0) followed by one daily tablet for the following 09 days. Albendazole 200 mg oral tablets: One tablet right after randomization (Day 0) followed by one daily tablet for the following 04 days. Vitamin C 50 mg oral tablets: Tablets started right after randomization (Day 0; 130mcg/ kg dosing), administered once a day for 05 consecutive days.

Primary Outcome Measure Information:

Title

COVID-19 disease progression

Description

This is a composite endpoint of moderate, severe or critical COVID-19 and Emergency Room attendace or hospitalization, or death

Time Frame

Up to 14 days after administration of investigational medicinal product (IMP)

Title

SARS-CoV-2 viral load

Description

Reduction in SARS-CoV-2 viral load in nasopharyngeal swabs at day 7 after start of treatment, as determined by RT-qPCR

Time Frame

Up to 7 days after administration of IMP

Secondary Outcome Measure Information:

Title

COVID-19 WHO Clinical progression scale score

Description

Change in COVID-19 WHO Clinical progression scale score

Time Frame

Up to 14 days after administration of IMP

Title

Adverse Events

Description

Incidence of Adverse Events

Time Frame

Up to 14 days after administration of IMP

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

99 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Adult male or female individuals of ≥18 years old. In women of childbearing potential, negative pregnancy test at inclusion/baseline visit. 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. 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. Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study. Has understood the information provided and capable of giving informed consent. Exclusion Criteria: If female, pregnant or breastfeeding, or planning a pregnancy during the study. 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. Severe or critical COVID-19, as defined per NIH: 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%. Critical COVID-19: respiratory failure, septic shock, and/or multiple organ dysfunction. History of previous confirmed SARS-CoV-2 infection. History of significantly abnormal liver function (Child Pugh C). History of chronic kidney disease (CKD) ≥ stage 4 or need of dialysis treatment. Any pre-existing condition that increases risk of thrombosis. History of allergic reactions to ivermectin, fluoxetine, prednisolone, or vitamins C, albendazole, any of its excipients. 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. Phenytoin Tricyclic antidepressants Antipsychotics: phenothiazines (i.e., chlorpromazine) haloperidol and most atypical (i.e., amitriptyline, aripiprazole, brexpiprazole, risperidone). Donepezil Tamoxifen Antiarrhytmics: propafenone, flecainide Amphetamine Concomitant use of SSRIs, SNRIs, or tricyclic antidepressants, linezolid, or methylene blue (rationale: increased risk of serotonin syndrome or TCA overdose). Concomitant use of drugs that could prolong the QT interval: Specific antipsychotics: ziprasidone, iloperidone, chlorpromazine, mesoridazine, droperidol Specific antibiotics: erythromycin, gatifloxacin, moxifloxacin, sparfloxacin Class 1A antiarrhytmics: amiodarone, sotalol Concomitant use of donepezil (S1R agonist) or sertraline (S1R antagonist) Uncontrolled psychiatric disorders, or suicidal ideation. Inability to consent and/or comply with study protocol, in the opinion of the investigator.

12. IPD Sharing Statement

Learn more about this trial

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

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