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

  • STATUS
    Recruiting
  • End date
    Nov 1, 2023
  • participants needed
    6246
  • sponsor
    Cardresearch
Updated on 24 July 2022

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.

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:

  1. 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.
  2. 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.

Details
Condition Covid19, SARS-Associated Coronavirus
Treatment Placebo, Metformin Extended Release Oral Tablet, Peginterferon Lambda-1a, Ivermectin Tablets, Fluvoxamine Maleate 100 MG [Luvox], Ivermectin oral tablets or sublingual waffles, Doxazosin 2 Mg Oral Tablet, Ivermectin 06 mg Oral Tablet, Peginterferon Beta-1A Prefilled Syringe, Budesonide Powder, Placebo (mild disease), Placebo (SpO2 < 94%), Fluoxetine 20 MG
Clinical Study IdentifierNCT04727424
SponsorCardresearch
Last Modified on24 July 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

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)
Willingness to use the proposed investigative treatment and follow the protocol-related procedures foreseen in the research
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
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

Patients with acute respiratory symptoms due to other causes
Exclusion criteria applicable to injectable medication arms
Exclusion criteria applicable to 10-day treatment arms
Pregnant or breastfeeding patients
Chronic corticosteroid use with equivalent prednisone doses of > 40 mg/day
Selegiline, Isocarboxazid, moclobemide
Diagnostic test for negative SARS-CoV2 associated with acute flu symptoms (patient
History of seizures in the last month or uncontrolled seizures
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
Dyspnea secondary to other acute and chronic respiratory causes or infections (eg
decompensated COPD, Acute bronchitis, Pneumonia other than viral, Primary pulmonary
Inability to use the drugs and formulations provided for in this research
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
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
5 mEq/L
Severe organ damage that requires resuscitation and ongoing treatment
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)
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
Patients with severe psychiatric disorders - schizophrenia, uncontrolled bipolar
disorders, major depression with suicidal ideation
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
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
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