A Multicenter, Prospective, Adaptive, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Effect of Fluvoxamine Plus Budesonide, Fluoxetine Plus Budesonide and Spirulin Platensis, in High Risk Patients With Mild COVID-19
Overview
- Phase
- Phase 3
- Intervention
- Budesonide Powder
- Conditions
- Covid19
- Sponsor
- Cardresearch
- Enrollment
- 7819
- Locations
- 12
- Primary Endpoint
- 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)
- Status
- Recruiting
- Last Updated
- last year
Overview
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 Spirulin Platensis 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 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).
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- •Negative diagnostic test for SARS-CoV2 associated with acute flu-like symptoms (patients with a negative test taken early and becoming positive a few days later are eligible, as long as they are \< 07 days from the onset of flu-like 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 (e.g. decompensated COPD, Acute bronchitis, Pneumonia other than viral, Primary pulmonary arterial hypertension);
- •Patients requiring hospitalization due to COVID-19 or SpO2 ≤ 93%.
- •Exclusion criteria applicable to the 7-day treatment arms:
- •Abnormal findings on physical examination: Respiratory rate ≥ 25 irm; blood pressure \< 90/ 60 mmHg or \> 160/ 100 mmHg; Weight \< 45 kg; recent episodes of vomiting in the last 24 hours or diarrhea \> 3 episodes in the last 24 hours or serum potassium below 3.5 mEq/L.
- •Serious injury to any organ that requires resuscitation and continuous treatment.
- •Use of chronic systemic corticosteroid therapy with prednisone equivalent doses of \> 40 mg/day
- •Ongoing immunosuppressive treatment
Arms & Interventions
Fluvoxamine Maleate + Budesonide Inhalation powder
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 one puff of 400 mcg BID for the following 09 days
Intervention: Budesonide Powder
Fluvoxamine Maleate + Budesonide Inhalation powder
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 one puff of 400 mcg BID for the following 09 days
Intervention: Placebo
Spirulin Platensis
Spirulin Platensis 500mg oral tablets Two tablets right after randomization (day 0) followed by 1.000mg (two tablets) BID for the following 10 days.
Intervention: Spirulin Platensis
Spirulin Platensis
Spirulin Platensis 500mg oral tablets Two tablets right after randomization (day 0) followed by 1.000mg (two tablets) BID for the following 10 days.
Intervention: Placebo
Fluoxetine + Budesonide Inhalation powder
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 one puff of 400 mcg BID for the following 06 days
Intervention: Fluoxetine 20 MG
Fluoxetine + Budesonide Inhalation powder
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 one puff of 400 mcg BID for the following 06 days
Intervention: Placebo
Placebo
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)
Intervention: Spirulin Platensis
Placebo
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)
Intervention: Budesonide Powder
Placebo
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)
Intervention: Fluoxetine 20 MG
Outcomes
Primary Outcomes
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)
Time Frame: 28 days
Hospitalization due to COVID-19 progression and related complications
Rate of fluvoxamine + budesonide, fluoxetine + budesonide, Spirulin platensis in changing SPO2 ≤ 93% after randomization
Time Frame: 28 days
Reduction of SPO2 ≤ 93% after randomization
Rate of fluvoxamine + budesonide, fluoxetine + budesonide, Spirulin platensis in emergency care visits due to the worsening of COVID-19;
Time Frame: 28 days
Evaluation of emergency visits due to progression of COVID-19 symptoms and/or ocmplications
Secondary Outcomes
- Number of days on hospitalizations(Randomization through day 28)
- Number of days with respiratory symptoms since randomization(Randomization through day 28)
- Number of days on Mechanical Ventilator(Randomization through day 28)
- Health and Functioning after COVID-19 disease(Day 14 and Day 28)
- Numbers of days with respiratory symptoms on WURSS-21 scale after randomization(Randomization through day 28)
- Time to symptom resolution(randomization through day 28)
- Adherence of Study drug(Randomization through day 10)
- Time to clinical changes (up to 28 days of randomization), defined as greater than 50% symptoms changing in reference to baseline symptoms.(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.(Randomization through day 28)
- Rate of all-cause hospitalizations(Randomization through day 28)
- Rate of COVID-19 related hospitalizations(Randomization through day 28)
- Number of Days on Intensive Care Unit(Randomization through day 28)