search
Back to results

Repurposed Approved and Under Development Therapies for Patients With Early-Onset COVID-19 and Mild Symptoms

Primary Purpose

Covid19, SARS-Associated Coronavirus

Status
Recruiting
Phase
Phase 3
Locations
Brazil
Study Type
Interventional
Intervention
Fluvoxamine Maleate 100 MG [Luvox]
Budesonide Powder
Placebo (mild disease)
Peginterferon Lambda-1a
Fluoxetine 20 MG
Sponsored by
Cardresearch
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Covid19 focused on measuring COVID-19, Randomized study, Fluvoxamine, Peginterferon Lambda, Budesonide, Fluoxetine

Eligibility Criteria

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

A - Inclusion Criteria (except fluoxetine + budesonide and paracetamol arms):

  1. Patients over 18 years old with the ability to provide free and informed consent
  2. Acute Flu-Like symptoms < 07 days.
  3. Patients with at least ONE enhancement criteria:

    1. Age > 50 years.
    2. Diabetes mellitus requiring oral medication or insulin.
    3. Systemic arterial hypertension requiring at least 01 oral medication for BP control.
    4. Known cardiovascular diseases (heart failure, congenital heart disease, valvar heart valve disease, coronary artery disease, cardiomyopathies).
    5. Symptomatic lung disease (emphysema, chronic bronchitis).
    6. Symptomatic asthma patients requiring chronic use of agents for control of symptoms.
    7. Fever > 38 C at baseline.
    8. Obesity, defined as BMI> 30 kg / m2 body weight.
    9. Transplanted patients.
    10. Patient with stage IV chronic kidney disease or on dialysis.
    11. Immunosuppressed patients/ using corticosteroid therapy (equivalent to maximum 10 mg of prednisone per day) and/ or immunosuppressive therapy).
    12. Patients with a history of cancer in the last 05 years or undergoing treatment of a current cancer.
    13. Chronic renal disease KDIGO IV or End-Stage Renal Disease on chronic ambulatory renal replacement therapy.
    14. Patients with important limitation of daily activities due to: Dyspnea, chest pain myalgia (limited to 25% of all randomizations).
  4. Patient with positive rapid test for SARS-CoV2 antigen performed on occasion of the screening or patient with a positive SARS-CoV2 diagnostic test within 07 days of the onset of symptoms.
  5. Willingness to use the proposed investigative treatment and follow the protocol-related procedures foreseen in the research.
  6. Specific inclusion criteria for the fluvoxamine arm: Present significant dyspnea, arterial hypotension, severe dehydration or SpO2 between 85 to 93% in room air at admission and medical decision to discharge patient home, with an observation period at ER not exceeding 12 hours.

B - Inclusion criteria for the Fluoxetine + Budesonide combination arm (07 days of treatment - partnership with the "ANTICOV Consortium"):

  1. Patients over 18 years of age with the ability to provide free and informed consent.
  2. Patients treated at a Basic Health Unit of the Unified Health System (SUS) or patients treated at emergency care units of the SUS or supplementary medicine with an acute clinical condition compatible with COVID 19.
  3. Patients over 18 years of age and a history of at least ONE of the following criteria.

    1. Diabetes mellitus, heart disease, chronic kidney disease, chronic obstructive pulmonary disease, cerebrovascular diseases or patients considered to be underweight or overweight according to the investigator's judgment (BMI ≤ 16 or BMI > 25).

      OR

    2. Individuals aged ≥ 60 years without co-morbidities.
  4. COVID-19 confirmed by molecular or antigenic test for SARS-CoV-2 within up to 24 hours prior to screening and a maximum of 2 days after sample collection.
  5. Viral syndrome with or without pneumonia and arterial O2 saturation > 94%.
  6. Signing the Free and Informed Consent Form before any research procedures.
  7. Willingness to use the proposed investigational treatment and follow the procedures provided for in the research.

Exclusion Criteria:

  1. Diagnostic test for negative SARS-CoV2 associated with acute flu symptoms (patient with a negative test collected early and becomes positive a few days later is eligible, as long as it is < 07 days since the onset of flu symptoms).
  2. Patients with an acute respiratory condition compatible with COVID-19 treated in the primary care network and with a decision to be hospitalized.
  3. Patients with acute respiratory symptoms due to other causes.
  4. Dyspnea secondary to other acute and chronic respiratory causes or infections (eg, decompensated COPD, Acute bronchitis, Pneumonia other than viral, Primary pulmonary arterial hypertension).
  5. Patients requiring hospitalization due to COVID-19 or SpO2 ≤ 93%. NOTE: Patients allocated to the fluvoxamine arm alone may be included if SpO2 is below 94%, with no evidence of acute respiratory failure, provided that the attending physician decides to discharge the unit and continue treatment on an outpatient basis.
  6. Exclusion criteria applicable to injectable medication arms:

    a. Patients on chronic use of prednisone, prednisolone or other corticosteroids with doses > 10 mg/day equivalent to prednisone.

  7. Exclusion criteria applicable to 07-day treatment arms:

    1. Abnormal findings on physical examination: Respiratory rate ≥ 25 sisters; blood pressure < 90/60 mmHg or > 160/100 mmHg; Weight < 45 kg; recent episodes of vomiting within the last 24 hours or recurrent diarrhea or serum potassium below 3.5 mEq/L.
    2. Severe organ damage that requires resuscitation and ongoing treatment.
    3. Chronic corticosteroid use with equivalent prednisone doses of > 40 mg/day
    4. Immunosuppressive treatment in progress
    5. History of known pulmonary arterial hypertension or pulmonary fibrosis
    6. Patients who have received a previous dose of SARS-CoV-2 vaccine
    7. Use of serotonin reuptake inhibitors (all).
  8. Exclusion criteria applicable to 10-day treatment arms:

    1. Chronic use of serotonin reuptake inhibitors other than sertraline
    2. Chronic corticosteroid use with equivalent prednisone doses of > 40 mg/day;
  9. Continued use of monoamine oxidative inhibitors (MAOI): Phenelzine, Tranylcypromine, Selegiline, Isocarboxazid, moclobemide.
  10. Patients with severe psychiatric disorders - schizophrenia, uncontrolled bipolar disorders, major depression with suicidal ideation.
  11. Pregnant or breastfeeding patients.
  12. History of severe ventricular cardiac arrhythmia (Ventricular tachycardia, recovered ventricular fibrillation patients) or Long QT Syndrome.
  13. Known history of decompensated heart failure (NYHA III or IV), recent myocardial infarction (event < 90 days of screening), unstable angina, recent coronary bypass surgery (procedure < 90 days of screening), recent stroke ( event < 90 days from screening), symptomatic carotid disease, or moderate to severe mitral or aortic stenosis.
  14. Surgical procedure or hospitalization planned (for other indications) to occur during treatment or up to 5 days after the last dose of study medication.
  15. Current daily and/or uncontrolled alcohol consumption, which, in the investigator's view, could compromise participation in the study.
  16. History of seizures in the last month or uncontrolled seizures.
  17. Clinical history of moderate to severe hepatic impairment or hepatic cirrhosis with Child-Pugh C classification.
  18. Patients with known serious degenerative neurological diseases and/or serious mental illnesses as assessed by the investigator.
  19. Inability of the patient or representative to give consent or adhere to the procedures proposed in the protocol.
  20. Any clinical conditions, including psychiatric conditions, which, in the investigator's view, could prevent the use of research drugs.
  21. Known hypersensitivity and/or intolerance to Fluvoxamine, Budesonide, Pegylated Interferon Lambda and Fluoxetine.
  22. Use of drugs which have a known interaction with Fluvoxamine, Budesonide, Pegylated Interferon Lambda and Fluoxetine.
  23. Inability to use the drugs and formulations provided for in this research.

Sites / Locations

  • City of BetimRecruiting
  • Hospital e Maternidade Santa RitaRecruiting
  • City of Governador ValadaresRecruiting
  • City of IbiritéRecruiting
  • City of Nova LimaRecruiting
  • City of Santa LuziaRecruiting
  • City of Sete LagoasRecruiting
  • CARDRESEARCH - Cardiologia Assistencial e de PesquisaRecruiting
  • City of BrumadinhoRecruiting
  • City of IgarapéRecruiting
  • Centro Universitário FIPMOCRecruiting
  • Universidade Federal de Ouro PretoRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Active Comparator

Active Comparator

Placebo Comparator

Active Comparator

Active Comparator

Arm Label

Fluvoxamine Maleate + Budesonide Inhalation powder

Fluvoxamine Maleate

Placebo (mild disease)

Peginterferon Lambda

Fluxetine + Budesonide Inhalation powder

Arm Description

Fluvoxamine 100 mg oral tablets: One tablet after randomization (Day 0) followed by 100 mg BID for the following 09 days PLUS Budesonide Inhalation powder 400 mcg capsule: One 400 mcg capsule (inhalation) after randomization (Day 0) followed by 400 mcg BID for the following 09 days

Fluvoxamine 100 mg oral tablets: One tablet after randomization (Day 0) followed by 100 mg BID for the following 09 days

Placebo SC normal saline syringe (single day schedule): Matching syringes containing 0,5 ml normal saline administered by SC route after randomization Day 0 (single dose SC). OR Placebo oral tablets (10-day schedule): Matching tablets started after randomization using the dosing regimen of 01 tablet every 12 hs starting at Randomization Day (Day 0) until end of Day 09 (total of 10 day schedule) PLUS Placebo Inhalation Therapy: One dosing (inhalation) right after randomization (Day 0) followed by one dose BID for the following 09 days OR Paracetamol (07-day schedule - active comparator): Paracetamol 500 mg tablets started after randomization using the dosing regimen of 01 tablet BID starting at Rand. Day (Day 0) until end of Day 06 (total of 07 days schedule) OR Placebo oral tablets (10-day schedule for patients with SPO2 < 94%): One tablet after randomization (Day 0) followed by 01 tablet BID for the following 09 days (total of 10 days schedule)

Peginterferon Lambda 180 mcg syringe: One syringe of Peginterferon Lambda will be administered by SC route just after randomization (Day 0 - single dose SC administration).

Fluoxetine 20 mg oral tablets: Two tablets right after randomization (Day 0) followed by 40 mg MID for the following 06 days PLUS Budesonide Inhalation powder 400 mcg capsule: One 400 mcg capsule (inhalation) right after randomization (Day 0) followed by 400 mcg BID for the following 06 days

Outcomes

Primary Outcome Measures

Rate of fluvoxamine + budesonide, fluoxetine + budesonide, peginterferon Lambda, fluvoxamine in changing the need for emergency care AND observation for more than 06 hours due to the worsening of COVID-19;
Evaluation of emergency visits and observation unit stay > 06 hours
Rate of fluvoxamine + budesonide, fluoxetine + budesonide, peginterferon Lambda and fluvoxamine in changing the need for Hospitalization due to COVID-19 progression and related complications, including lower respiratory tract infection (LRTI)
Hospitalization due to COVID-19 progression and related complications
Rate of fluvoxamine + budesonide, fluoxetine + budesonide, peginterferon Lambda and fluvoxamine in changing the COVID-19 associated mortality.
Mortality due to COVID-19 associated complications

Secondary Outcome Measures

Change in viral load on day 03 and 07 after randomization (interferon lambda arm)
Viral load
Time to clinical changes (up to 28 days of randomization), defined as greater than 50% symptoms changing in reference to baseline symptoms)
time to > 50% clinical symptoms changes as reported on baseline visit (self reported)
Time to clinical failure, defined as time to need for hospitalization due to the clinical progression of COVID-19 or associated complications.
Time to hospitalization
Number of days with respiratory symptoms since randomization
Days with symptoms
Rate of all-cause hospitalizations
All cause hospitalizations
Rate of COVID-19 related hospitalizations
COVID-19 hospitalizations
Number of days on Mechanical Ventilator
Number of days on mechanical Ventilator
Number of Days on Intensive Care Unit
Number of days on Intensive Care Unit
Number of days on hospitalizations
Number of days on Hospitalization
Health and Functioning after COVID-19 disease
Self evaluation of health functioning post COVID using Promis Global Health Score. Short term scale is a 10 item patient-reported questionnaire using response options as a 5-point and one 11 point rating scale. Higher scores means better global health.
WHO ordinal scale for clinical improvement
An 8 item Ordinal Scale for clinical status on COVID-19. Higher numbers means worse clinical status.
Number of days on respiratory Symptoms
Number of days on respiratory symptoms
Adherence of Study drug
Percentage of adherence on Study drug

Full Information

First Posted
January 25, 2021
Last Updated
July 3, 2022
Sponsor
Cardresearch
Collaborators
Cytel Inc., McMaster University, Fastgrants, Eiger BioPharmaceuticals, RainWater Foundation
search

1. Study Identification

Unique Protocol Identification Number
NCT04727424
Brief Title
Repurposed Approved and Under Development Therapies for Patients With Early-Onset COVID-19 and Mild Symptoms
Official Title
A Multicenter, Prospective, Adaptive, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Effect of Interferon Lambda 1A, Fluvoxamina + Budesonida, Fluoxetina + Budesonida in Mild COVID-19 and High Risk of Complications
Study Type
Interventional

2. Study Status

Record Verification Date
January 2022
Overall Recruitment Status
Recruiting
Study Start Date
January 19, 2021 (Actual)
Primary Completion Date
October 1, 2023 (Anticipated)
Study Completion Date
November 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cardresearch
Collaborators
Cytel Inc., McMaster University, Fastgrants, Eiger BioPharmaceuticals, RainWater Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The COVID-19 pandemic has been characterized by high morbidity and mortality, especially in certain subgroups of patients. To date, no treatment has been shown to be effective in patients with early-onset disease and mild symptoms. Experimental studies have demonstrated a potential anti-inflammatory role of Fluvoxamine, Fluoxetine, Budesonide and Pegilatrd Interferon Lambda in SARS-CoV-2 infections and observational studies have suggested a reduced complications in patients with COVID-19 disease.
Detailed Description
In December 2019 a series of viral pneumonia cases were reported in the city of Wuhan, China and a new subtype of coronavirus has been identified as the causative agent of this condition. On February 11, 2000 the disease has been characterized as COVID-19 and on March 11 the World Health Organization (WHO) declared a state of worldwide pandemic. On January 25, 2021 there are 98,794,942 cases and 2,124,193 documented deaths (global case-fatality ratio of 2.15%). To date, no early treatment has been identified as effective in combating this disease which has been identified as with high morbidity and mortality. Epidemiological data suggest that despite development of vaccines we will have hundreds od thousands of cases in the next two years. Thus, we propose the prospective, double-blinded, randomized evaluation of potential therapies against SARS-CoV2 and some clinical evidence derived from observational studies on reducing complications if used early on the disease, before inflammatory cascade is fully activated. Important considerations on TOGETHER Trial: Vaccinated patients were proposed to be an exclusion criteria on amendment 3 which was received final National Ethics Committee (CONEP) decision letter number 4.747.755_E3 dated June 01, 2021. We evaluated vaccination data and outcomes on two large cities involving 150.000 individuals and based on these results we submitted to the IRB a notification request to withdraw the exclusion criteria 4 (vaccination > 14 days) on July 14, 2021, which was granted. The amendment 5 proposed a collaborative partnership with ANTICOV Consortia and incorporating the fluoxetine + budesonide and its active comparator (paracetamol) arms, as per ANTICOV protocol WHO ERC approval version 13.0. These generated data will be analyzed along with ANTICOV fluoxetine + budesonide and paracetamol arms.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid19, SARS-Associated Coronavirus
Keywords
COVID-19, Randomized study, Fluvoxamine, Peginterferon Lambda, Budesonide, Fluoxetine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
TOGETHER trial is a Multiplatform, adaptive trial started on 20 Jan 2021. this description is as per amendment five with final Brazilian National Ethics Committee final decision letter issued on 27 January 2022. Patients with mild disease will be screened at primary and secondary care public health services and randomly allocated to one of four treatment arms in a 1:1:1:1 ratio, as per described in detail in approved protocol version 6.0 dated 03 JAN 2022. Fluvoxamine + Budesonide Fluoxetine + Budesonide Peginterferon Lambda Placebo Patients with SpO2 < 94% will be randomly allocated to one of two arms in a 1: ! ratio: Fluvoxamine Placebo We will use a centralized random allocation schedule, generated by computer and stratified by site and age.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
The investigational medical product will be packaged in similar bottles by a third party who will keep the allocation confidential until the end of the study. The bottles will be sealed and identified as "Research Product with no commercial value" and coded. They will be randomly allocated among the participants using a centralized randomization system The research subjects, medical assistance, administrative and health staff will not have access to the contents of the bottles. All arms will have a placebo counterpart with same dose schedule. All planned Data and Safety Monitoring Board (DSMB) interim analysis will be blinded. If needed a unblinded statistician will be provided if DSMB decides to stop any arm. At the end of the study, or early termination as per DMSB interim analysis plan, the arms will then be identified.
Allocation
Randomized
Enrollment
6246 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Fluvoxamine Maleate + Budesonide Inhalation powder
Arm Type
Active Comparator
Arm Description
Fluvoxamine 100 mg oral tablets: One tablet after randomization (Day 0) followed by 100 mg BID for the following 09 days PLUS Budesonide Inhalation powder 400 mcg capsule: One 400 mcg capsule (inhalation) after randomization (Day 0) followed by 400 mcg BID for the following 09 days
Arm Title
Fluvoxamine Maleate
Arm Type
Active Comparator
Arm Description
Fluvoxamine 100 mg oral tablets: One tablet after randomization (Day 0) followed by 100 mg BID for the following 09 days
Arm Title
Placebo (mild disease)
Arm Type
Placebo Comparator
Arm Description
Placebo SC normal saline syringe (single day schedule): Matching syringes containing 0,5 ml normal saline administered by SC route after randomization Day 0 (single dose SC). OR Placebo oral tablets (10-day schedule): Matching tablets started after randomization using the dosing regimen of 01 tablet every 12 hs starting at Randomization Day (Day 0) until end of Day 09 (total of 10 day schedule) PLUS Placebo Inhalation Therapy: One dosing (inhalation) right after randomization (Day 0) followed by one dose BID for the following 09 days OR Paracetamol (07-day schedule - active comparator): Paracetamol 500 mg tablets started after randomization using the dosing regimen of 01 tablet BID starting at Rand. Day (Day 0) until end of Day 06 (total of 07 days schedule) OR Placebo oral tablets (10-day schedule for patients with SPO2 < 94%): One tablet after randomization (Day 0) followed by 01 tablet BID for the following 09 days (total of 10 days schedule)
Arm Title
Peginterferon Lambda
Arm Type
Active Comparator
Arm Description
Peginterferon Lambda 180 mcg syringe: One syringe of Peginterferon Lambda will be administered by SC route just after randomization (Day 0 - single dose SC administration).
Arm Title
Fluxetine + Budesonide Inhalation powder
Arm Type
Active Comparator
Arm Description
Fluoxetine 20 mg oral tablets: Two tablets right after randomization (Day 0) followed by 40 mg MID for the following 06 days PLUS Budesonide Inhalation powder 400 mcg capsule: One 400 mcg capsule (inhalation) right after randomization (Day 0) followed by 400 mcg BID for the following 06 days
Intervention Type
Drug
Intervention Name(s)
Fluvoxamine Maleate 100 MG [Luvox]
Intervention Description
One tablet every 12 hours since randomization through day 09.
Intervention Type
Drug
Intervention Name(s)
Budesonide Powder
Other Intervention Name(s)
Fluvoxamine Maleate 100 MG [Luvox]
Intervention Description
One Fluvoxamine tablet every 12 hours since randomization through day 09. PLUS 01 Budesonide powder (inhalation) every 12 hours since randomization through day 09.
Intervention Type
Drug
Intervention Name(s)
Placebo (mild disease)
Intervention Description
Placebo SC normal saline syringe (single day schedule): Matching syringes containing 0,5 ml normal saline administered by SC route after randomization Day 0 (single dose SC). OR Placebo oral tablets (10-day schedule): Matching tablets started after randomization using the dosing regimen of 01 tablet every 12 hs starting at Randomization Day (Day 0) until end of Day 09 (total of 10 day schedule) PLUS Placebo Inhalation Therapy: One dosing (inhalation) right after randomization (Day 0) followed by one dose BID for the following 09 days OR Paracetamol (07-day schedule - active comparator): Paracetamol 500 mg tablets started after randomization using the dosing regimen of 01 tablet BID starting at Rand. Day (Day 0) until end of Day 06 (total of 07 days schedule) OR Placebo oral tablets (10-day schedule for patients with SPO2 < 94%): One tablet after randomization (Day 0) followed by 01 tablet BID for the following 09 days (total of 10 days schedule)
Intervention Type
Drug
Intervention Name(s)
Peginterferon Lambda-1a
Intervention Description
One syringe of 180 mcg of Peginterferon Lambda SC right after randomization Day 0 (single dose SC administration).
Intervention Type
Drug
Intervention Name(s)
Fluoxetine 20 MG
Intervention Description
Two Fluoxetine tablets every day starting just after randomization through day 07. PLUS 01 Budesonide powder (inhalation) every 12 hours since randomization through day 07.
Primary Outcome Measure Information:
Title
Rate of fluvoxamine + budesonide, fluoxetine + budesonide, peginterferon Lambda, fluvoxamine in changing the need for emergency care AND observation for more than 06 hours due to the worsening of COVID-19;
Description
Evaluation of emergency visits and observation unit stay > 06 hours
Time Frame
28 days
Title
Rate of fluvoxamine + budesonide, fluoxetine + budesonide, peginterferon Lambda and fluvoxamine in changing the need for Hospitalization due to COVID-19 progression and related complications, including lower respiratory tract infection (LRTI)
Description
Hospitalization due to COVID-19 progression and related complications
Time Frame
28 days
Title
Rate of fluvoxamine + budesonide, fluoxetine + budesonide, peginterferon Lambda and fluvoxamine in changing the COVID-19 associated mortality.
Description
Mortality due to COVID-19 associated complications
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Change in viral load on day 03 and 07 after randomization (interferon lambda arm)
Description
Viral load
Time Frame
Day 3 and Day 7
Title
Time to clinical changes (up to 28 days of randomization), defined as greater than 50% symptoms changing in reference to baseline symptoms)
Description
time to > 50% clinical symptoms changes as reported on baseline visit (self reported)
Time Frame
Randomization through day 28
Title
Time to clinical failure, defined as time to need for hospitalization due to the clinical progression of COVID-19 or associated complications.
Description
Time to hospitalization
Time Frame
Randomization through day 28
Title
Number of days with respiratory symptoms since randomization
Description
Days with symptoms
Time Frame
Randomization through day 28
Title
Rate of all-cause hospitalizations
Description
All cause hospitalizations
Time Frame
Randomization through day 28
Title
Rate of COVID-19 related hospitalizations
Description
COVID-19 hospitalizations
Time Frame
Randomization through day 28
Title
Number of days on Mechanical Ventilator
Description
Number of days on mechanical Ventilator
Time Frame
Randomization through day 28
Title
Number of Days on Intensive Care Unit
Description
Number of days on Intensive Care Unit
Time Frame
Randomization through day 28
Title
Number of days on hospitalizations
Description
Number of days on Hospitalization
Time Frame
Randomization through day 28
Title
Health and Functioning after COVID-19 disease
Description
Self evaluation of health functioning post COVID using Promis Global Health Score. Short term scale is a 10 item patient-reported questionnaire using response options as a 5-point and one 11 point rating scale. Higher scores means better global health.
Time Frame
Day 14 and Day 28
Title
WHO ordinal scale for clinical improvement
Description
An 8 item Ordinal Scale for clinical status on COVID-19. Higher numbers means worse clinical status.
Time Frame
Randomization through day 28
Title
Number of days on respiratory Symptoms
Description
Number of days on respiratory symptoms
Time Frame
randomization through day 28
Title
Adherence of Study drug
Description
Percentage of adherence on Study drug
Time Frame
Randomization through day 14

10. Eligibility

Sex
All
Gender Based
Yes
Gender Eligibility Description
Gender will be assumed as patient self-reported
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
A - Inclusion Criteria (except fluoxetine + budesonide and paracetamol arms): Patients over 18 years old with the ability to provide free and informed consent Acute Flu-Like symptoms < 07 days. Patients with at least ONE enhancement criteria: Age > 50 years. Diabetes mellitus requiring oral medication or insulin. Systemic arterial hypertension requiring at least 01 oral medication for BP control. Known cardiovascular diseases (heart failure, congenital heart disease, valvar heart valve disease, coronary artery disease, cardiomyopathies). Symptomatic lung disease (emphysema, chronic bronchitis). Symptomatic asthma patients requiring chronic use of agents for control of symptoms. Fever > 38 C at baseline. Obesity, defined as BMI> 30 kg / m2 body weight. Transplanted patients. Patient with stage IV chronic kidney disease or on dialysis. Immunosuppressed patients/ using corticosteroid therapy (equivalent to maximum 10 mg of prednisone per day) and/ or immunosuppressive therapy). Patients with a history of cancer in the last 05 years or undergoing treatment of a current cancer. Chronic renal disease KDIGO IV or End-Stage Renal Disease on chronic ambulatory renal replacement therapy. Patients with important limitation of daily activities due to: Dyspnea, chest pain myalgia (limited to 25% of all randomizations). Patient with positive rapid test for SARS-CoV2 antigen performed on occasion of the screening or patient with a positive SARS-CoV2 diagnostic test within 07 days of the onset of symptoms. Willingness to use the proposed investigative treatment and follow the protocol-related procedures foreseen in the research. Specific inclusion criteria for the fluvoxamine arm: Present significant dyspnea, arterial hypotension, severe dehydration or SpO2 between 85 to 93% in room air at admission and medical decision to discharge patient home, with an observation period at ER not exceeding 12 hours. B - Inclusion criteria for the Fluoxetine + Budesonide combination arm (07 days of treatment - partnership with the "ANTICOV Consortium"): Patients over 18 years of age with the ability to provide free and informed consent. Patients treated at a Basic Health Unit of the Unified Health System (SUS) or patients treated at emergency care units of the SUS or supplementary medicine with an acute clinical condition compatible with COVID 19. Patients over 18 years of age and a history of at least ONE of the following criteria. Diabetes mellitus, heart disease, chronic kidney disease, chronic obstructive pulmonary disease, cerebrovascular diseases or patients considered to be underweight or overweight according to the investigator's judgment (BMI ≤ 16 or BMI > 25). OR Individuals aged ≥ 60 years without co-morbidities. COVID-19 confirmed by molecular or antigenic test for SARS-CoV-2 within up to 24 hours prior to screening and a maximum of 2 days after sample collection. Viral syndrome with or without pneumonia and arterial O2 saturation > 94%. Signing the Free and Informed Consent Form before any research procedures. Willingness to use the proposed investigational treatment and follow the procedures provided for in the research. Exclusion Criteria: Diagnostic test for negative SARS-CoV2 associated with acute flu symptoms (patient with a negative test collected early and becomes positive a few days later is eligible, as long as it is < 07 days since the onset of flu symptoms). Patients with an acute respiratory condition compatible with COVID-19 treated in the primary care network and with a decision to be hospitalized. Patients with acute respiratory symptoms due to other causes. Dyspnea secondary to other acute and chronic respiratory causes or infections (eg, decompensated COPD, Acute bronchitis, Pneumonia other than viral, Primary pulmonary arterial hypertension). Patients requiring hospitalization due to COVID-19 or SpO2 ≤ 93%. NOTE: Patients allocated to the fluvoxamine arm alone may be included if SpO2 is below 94%, with no evidence of acute respiratory failure, provided that the attending physician decides to discharge the unit and continue treatment on an outpatient basis. Exclusion criteria applicable to injectable medication arms: a. Patients on chronic use of prednisone, prednisolone or other corticosteroids with doses > 10 mg/day equivalent to prednisone. Exclusion criteria applicable to 07-day treatment arms: Abnormal findings on physical examination: Respiratory rate ≥ 25 sisters; blood pressure < 90/60 mmHg or > 160/100 mmHg; Weight < 45 kg; recent episodes of vomiting within the last 24 hours or recurrent diarrhea or serum potassium below 3.5 mEq/L. Severe organ damage that requires resuscitation and ongoing treatment. Chronic corticosteroid use with equivalent prednisone doses of > 40 mg/day Immunosuppressive treatment in progress History of known pulmonary arterial hypertension or pulmonary fibrosis Patients who have received a previous dose of SARS-CoV-2 vaccine Use of serotonin reuptake inhibitors (all). Exclusion criteria applicable to 10-day treatment arms: Chronic use of serotonin reuptake inhibitors other than sertraline Chronic corticosteroid use with equivalent prednisone doses of > 40 mg/day; Continued use of monoamine oxidative inhibitors (MAOI): Phenelzine, Tranylcypromine, Selegiline, Isocarboxazid, moclobemide. Patients with severe psychiatric disorders - schizophrenia, uncontrolled bipolar disorders, major depression with suicidal ideation. Pregnant or breastfeeding patients. History of severe ventricular cardiac arrhythmia (Ventricular tachycardia, recovered ventricular fibrillation patients) or Long QT Syndrome. Known history of decompensated heart failure (NYHA III or IV), recent myocardial infarction (event < 90 days of screening), unstable angina, recent coronary bypass surgery (procedure < 90 days of screening), recent stroke ( event < 90 days from screening), symptomatic carotid disease, or moderate to severe mitral or aortic stenosis. Surgical procedure or hospitalization planned (for other indications) to occur during treatment or up to 5 days after the last dose of study medication. Current daily and/or uncontrolled alcohol consumption, which, in the investigator's view, could compromise participation in the study. History of seizures in the last month or uncontrolled seizures. Clinical history of moderate to severe hepatic impairment or hepatic cirrhosis with Child-Pugh C classification. Patients with known serious degenerative neurological diseases and/or serious mental illnesses as assessed by the investigator. Inability of the patient or representative to give consent or adhere to the procedures proposed in the protocol. Any clinical conditions, including psychiatric conditions, which, in the investigator's view, could prevent the use of research drugs. Known hypersensitivity and/or intolerance to Fluvoxamine, Budesonide, Pegylated Interferon Lambda and Fluoxetine. Use of drugs which have a known interaction with Fluvoxamine, Budesonide, Pegylated Interferon Lambda and Fluoxetine. Inability to use the drugs and formulations provided for in this research.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Gilmar Reis, MD, PhD
Phone
+553132416574
Email
administrador@cardresearch.org
First Name & Middle Initial & Last Name or Official Title & Degree
Eduardo Santos, MD, PhD
Phone
+553132416574
Email
duduaugusto1@yahoo.com.br
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilmar Reis, MD,PhD.
Organizational Affiliation
Cardresearch - Cardiologia Assistencial e de Pesquisa
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Edward J Mills, FRCP
Organizational Affiliation
McMaster University
Official's Role
Study Director
Facility Information:
Facility Name
City of Betim
City
Betim
State/Province
MG
ZIP/Postal Code
32550770
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Daniela C Medeiros, MD,PhD
First Name & Middle Initial & Last Name & Degree
Tainara S Vieira
Facility Name
Hospital e Maternidade Santa Rita
City
Contagem
State/Province
MG
ZIP/Postal Code
32215000
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thiago S Ferreira, MD
Facility Name
City of Governador Valadares
City
Governador Valadares
State/Province
MG
ZIP/Postal Code
35010-000
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Adhemar DF Neto, MD, PhD
First Name & Middle Initial & Last Name & Degree
Marina L Marques, SC
Facility Name
City of Ibirité
City
Ibirité
State/Province
MG
ZIP/Postal Code
30240528
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aline Milagres, RN
First Name & Middle Initial & Last Name & Degree
Carla Silva, SC
Email
hsfapesq@cardresearch.org
Facility Name
City of Nova Lima
City
Nova Lima
State/Province
MG
ZIP/Postal Code
34000000
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Leticia F Costa, RN
First Name & Middle Initial & Last Name & Degree
Rosemary M Silva
Facility Name
City of Santa Luzia
City
Santa Luzia
State/Province
MG
ZIP/Postal Code
33105160
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eduardo Augusto SM Silva, MD, PhD
First Name & Middle Initial & Last Name & Degree
Vitoria HS Campos, SC
Facility Name
City of Sete Lagoas
City
Sete Lagoas
State/Province
MG
ZIP/Postal Code
35700-000
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vinicius A Correa, MD
First Name & Middle Initial & Last Name & Degree
Castilho Vitor Quirino, SC
Email
vitor-quirino@hotmail.com
Facility Name
CARDRESEARCH - Cardiologia Assistencial e de Pesquisa
City
Belo Horizonte
State/Province
Minas Gerais
ZIP/Postal Code
30150240
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Izabel Silva, SC
Phone
553132416574
Email
coordpesq@cardresearch.org
First Name & Middle Initial & Last Name & Degree
Gilmar Reis, MD,PhD
Facility Name
City of Brumadinho
City
Brumadinho
State/Province
Minas Gerais
ZIP/Postal Code
35.460-000
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eduardo D Calegari, MD
First Name & Middle Initial & Last Name & Degree
Eduardo Calegari, MD
Facility Name
City of Igarapé
City
Igarapé
State/Province
Minas Gerais
ZIP/Postal Code
32900-000
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Luciene B Ribeiro, RN
Phone
+55313657574
Facility Name
Centro Universitário FIPMOC
City
Montes Claros
State/Province
Minas Gerais
ZIP/Postal Code
39.408-007
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ana Maria, MD
First Name & Middle Initial & Last Name & Degree
Ana Maria R Nogueira, MD
First Name & Middle Initial & Last Name & Degree
Ana Paula FG Alvarenga, MD
Facility Name
Universidade Federal de Ouro Preto
City
Ouro Preto
State/Province
Minas Gerais
ZIP/Postal Code
35400000
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Leonardo CM Savassi, MD, PhD
Email
leosavassi@gmail.com
First Name & Middle Initial & Last Name & Degree
Leonardo Savassi, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Patient tables and main data.
IPD Sharing Time Frame
As of protocol termination
IPD Sharing Access Criteria
Upon request
Citations:
PubMed Identifier
32828137
Citation
Rayner CR, Dron L, Park JJH, Decloedt EH, Cotton MF, Niranjan V, Smith PF, Dodds MG, Brown F, Reis G, Wesche D, Mills EJ. Accelerating Clinical Evaluation of Repurposed Combination Therapies for COVID-19. Am J Trop Med Hyg. 2020 Oct;103(4):1364-1366. doi: 10.4269/ajtmh.20-0995.
Results Reference
background
PubMed Identifier
33865476
Citation
Park JJH, Mogg R, Smith GE, Nakimuli-Mpungu E, Jehan F, Rayner CR, Condo J, Decloedt EH, Nachega JB, Reis G, Mills EJ. How COVID-19 has fundamentally changed clinical research in global health. Lancet Glob Health. 2021 May;9(5):e711-e720. doi: 10.1016/S2214-109X(20)30542-8.
Results Reference
background
PubMed Identifier
34996047
Citation
Forrest JI, Rawat A, Duailibe F, Guo CM, Sprague S, McKay P, Reis G, Mills EJ. Resilient Clinical Trial Infrastructure in Response to the COVID-19 Pandemic: Lessons Learned from the TOGETHER Randomized Platform Clinical Trial. Am J Trop Med Hyg. 2022 Jan 7;106(2):389-393. doi: 10.4269/ajtmh.21-1202.
Results Reference
background
PubMed Identifier
35180413
Citation
Reis G, Mills E. Fluvoxamine for the treatment of COVID-19 - Author's reply. Lancet Glob Health. 2022 Mar;10(3):e333. doi: 10.1016/S2214-109X(21)00588-X. No abstract available.
Results Reference
background
PubMed Identifier
35294804
Citation
Thorlund K, Sheldrick K, Mills E. Molnupiravir for Covid-19 in Nonhospitalized Patients. N Engl J Med. 2022 Mar 31;386(13):e32. doi: 10.1056/NEJMc2201612. Epub 2022 Mar 16. No abstract available.
Results Reference
background
PubMed Identifier
34982138
Citation
Park JJH, Detry MA, Murthy S, Guyatt G, Mills EJ. How to Use and Interpret the Results of a Platform Trial: Users' Guide to the Medical Literature. JAMA. 2022 Jan 4;327(1):67-74. doi: 10.1001/jama.2021.22507.
Results Reference
background
PubMed Identifier
35445964
Citation
Jhuti D, Rawat A, Guo CM, Wilson LA, Mills EJ, Forrest JI. Interferon Treatments for SARS-CoV-2: Challenges and Opportunities. Infect Dis Ther. 2022 Jun;11(3):953-972. doi: 10.1007/s40121-022-00633-9. Epub 2022 Apr 21.
Results Reference
background
PubMed Identifier
34000408
Citation
Park JJH, Dron L, Mills EJ. Moving forward in clinical research with master protocols. Contemp Clin Trials. 2021 Jul;106:106438. doi: 10.1016/j.cct.2021.106438. Epub 2021 May 14.
Results Reference
background
PubMed Identifier
33865474
Citation
Park JJH, Ford N, Xavier D, Ashorn P, Grais RF, Bhutta ZA, Goossens H, Thorlund K, Socias ME, Mills EJ. Randomised trials at the level of the individual. Lancet Glob Health. 2021 May;9(5):e691-e700. doi: 10.1016/S2214-109X(20)30540-4.
Results Reference
background
PubMed Identifier
33236703
Citation
Lee Z, Rayner CR, Forrest JI, Nachega JB, Senchaudhuri E, Mills EJ. The Rise and Fall of Hydroxychloroquine for the Treatment and Prevention of COVID-19. Am J Trop Med Hyg. 2021 Jan;104(1):35-38. doi: 10.4269/ajtmh.20-1320.
Results Reference
background
PubMed Identifier
33684053
Citation
Dron L, Dillman A, Zoratti MJ, Haggstrom J, Mills EJ, Park JJH. Clinical Trial Data Sharing for COVID-19-Related Research. J Med Internet Res. 2021 Mar 12;23(3):e26718. doi: 10.2196/26718.
Results Reference
background
PubMed Identifier
33279656
Citation
Dillman A, Park JJH, Zoratti MJ, Zannat NE, Lee Z, Dron L, Hsu G, Smith G, Khakabimamaghani S, Harari O, Thorlund K, Mills EJ. Reporting and design of randomized controlled trials for COVID-19: A systematic review. Contemp Clin Trials. 2021 Feb;101:106239. doi: 10.1016/j.cct.2020.106239. Epub 2020 Dec 3.
Results Reference
background
PubMed Identifier
34717820
Citation
Reis G, Dos Santos Moreira-Silva EA, Silva DCM, Thabane L, Milagres AC, Ferreira TS, Dos Santos CVQ, de Souza Campos VH, Nogueira AMR, de Almeida APFG, Callegari ED, de Figueiredo Neto AD, Savassi LCM, Simplicio MIC, Ribeiro LB, Oliveira R, Harari O, Forrest JI, Ruton H, Sprague S, McKay P, Glushchenko AV, Rayner CR, Lenze EJ, Reiersen AM, Guyatt GH, Mills EJ; TOGETHER investigators. Effect of early treatment with fluvoxamine on risk of emergency care and hospitalisation among patients with COVID-19: the TOGETHER randomised, platform clinical trial. Lancet Glob Health. 2022 Jan;10(1):e42-e51. doi: 10.1016/S2214-109X(21)00448-4. Epub 2021 Oct 28. Erratum In: Lancet Glob Health. 2022 Apr;10(4):e481. Lancet Glob Health. 2022 Sep;10(9):e1246.
Results Reference
result
PubMed Identifier
34927127
Citation
Reis G, Dos Santos Moreira Silva EA, Medeiros Silva DC, Thabane L, Cruz Milagres A, Ferreira TS, Quirino Dos Santos CV, de Figueiredo Neto AD, Diniz Callegari E, Monteiro Savassi LC, Campos Simplicio MI, Barra Ribeiro L, Oliveira R, Harari O, Bailey H, Forrest JI, Glushchenko A, Sprague S, McKay P, Rayner CR, Ruton H, Guyatt GH, Mills EJ. Effect of early treatment with metformin on risk of emergency care and hospitalization among patients with COVID-19: The TOGETHER randomized platform clinical trial. Lancet Reg Health Am. 2022 Feb;6:100142. doi: 10.1016/j.lana.2021.100142. Epub 2021 Dec 14.
Results Reference
result
PubMed Identifier
35353979
Citation
Reis G, Silva EASM, Silva DCM, Thabane L, Milagres AC, Ferreira TS, Dos Santos CVQ, Campos VHS, Nogueira AMR, de Almeida APFG, Callegari ED, Neto ADF, Savassi LCM, Simplicio MIC, Ribeiro LB, Oliveira R, Harari O, Forrest JI, Ruton H, Sprague S, McKay P, Guo CM, Rowland-Yeo K, Guyatt GH, Boulware DR, Rayner CR, Mills EJ; TOGETHER Investigators. Effect of Early Treatment with Ivermectin among Patients with Covid-19. N Engl J Med. 2022 May 5;386(18):1721-1731. doi: 10.1056/NEJMoa2115869. Epub 2022 Mar 30.
Results Reference
result

Learn more about this trial

Repurposed Approved and Under Development Therapies for Patients With Early-Onset COVID-19 and Mild Symptoms

We'll reach out to this number within 24 hrs