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 Spirulin Platensis in SARS-CoV-2 infections and observational studies have suggested a reduced complications in patients with COVID-19 disease.
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 Adaptive Trial: 1. The Pegylated Lambda interferon arm was ended on early February 2022. 2. The Proposal of a new arm: Spirulin platensis. 3. The Modification on primary endpoints that will be effective only for new arms added to the trial (Spirulin platensis).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
7,819
Two tablets every 12 hours since randomization through day 09 following randomization
One Fluvoxamine tablet every 12 hours since randomization through day 09. PLUS 01 Budesonide powder (inhalation) every 12 hours since randomization through day 09.
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.
CARDRESEARCH - Cardiologia Assistencial e de Pesquisa
Belo Horizonte, Minas Gerais, Brazil
RECRUITINGCity of Betim
Betim, Minas Gerais, Brazil
Rate of fluvoxamine + budesonide, fluoxetine + budesonide, Spirulin platensis in emergency care visits due to the worsening of COVID-19;
Evaluation of emergency visits due to progression of COVID-19 symptoms and/or ocmplications
Time frame: 28 days
Rate of fluvoxamine + budesonide, fluoxetine + budesonide, Spirulin platensis 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
Time frame: 28 days
Rate of fluvoxamine + budesonide, fluoxetine + budesonide, Spirulin platensis in changing SPO2 ≤ 93% after randomization
Reduction of SPO2 ≤ 93% after randomization
Time frame: 28 days
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 frame: Randomization through day 28
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
Time frame: Randomization through day 28
Number of days with respiratory symptoms since randomization
Days with symptoms
Time frame: Randomization through day 28
Rate of all-cause hospitalizations
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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 puff) right after randomization (Day 0) followed by one puff 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 - ANTICOV Arm) OR Matching tablets started after randomization using the dosing regimen of 02 tablets every 12 hs starting at Randomization Day (Day 0) until end of Day 09 (total of 10 day schedule)
City of Brumadinho
Brumadinho, Minas Gerais, Brazil
NOT_YET_RECRUITINGHospital e Maternidade Santa Rita
Contagem, Minas Gerais, Brazil
RECRUITINGCity of Governador Valadares
Governador Valadares, Minas Gerais, Brazil
RECRUITINGCity of Ibirité
Ibirité, Minas Gerais, Brazil
RECRUITINGCity of Igarapé
Igarapé, Minas Gerais, Brazil
RECRUITINGCentro Universitário FIPMOC
Montes Claros, Minas Gerais, Brazil
RECRUITINGCity of Nova Lima
Nova Lima, Minas Gerais, Brazil
RECRUITINGUniversidade Federal de Ouro Preto
Ouro Preto, Minas Gerais, Brazil
RECRUITING...and 2 more locations
All cause hospitalizations
Time frame: Randomization through day 28
Rate of COVID-19 related hospitalizations
COVID-19 hospitalizations
Time frame: Randomization through day 28
Number of days on Mechanical Ventilator
Number of days on mechanical Ventilator
Time frame: Randomization through day 28
Number of Days on Intensive Care Unit
Number of days on Intensive Care Unit
Time frame: Randomization through day 28
Number of days on hospitalizations
Number of days on Hospitalization
Time frame: Randomization through day 28
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.
Time frame: Day 14 and Day 28
Numbers of days with respiratory symptoms on WURSS-21 scale after randomization
Numbers of days with respiratory symptoms on WURSS-21 scale after randomization
Time frame: Randomization through day 28
Time to symptom resolution
Time to improvement \> 50% of baseline symptomatology based on WURSS-21 Scale.
Time frame: randomization through day 28
Adherence of Study drug
Percentage of adherence on Study drug
Time frame: Randomization through day 10