Efficacy of Inhaled Therapies in the Treatment of Acute Symptoms Associated With COVID-19 (TRIVID)

Randomized, Open-label, Three Arms Study to Evaluate the Efficacy of Inhaled Therapies in the Treatment of Acute Symptoms Associated With COVID-19 and in the Prevention of the Use of Health Resources in Patients With ≥ 18 Years Old (TRIVID Study)

Introduction: SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), the new coronavirus, causes a disease called COVID-19 that can trigger aggressive inflammatory responses. In this sense, inhaled corticosteroid therapy (IC) has shown some favorable results in controlling the worsening of the disease, given that it has effects on pulmonary inflammation and can be an intervention to be used in the mild manifestations of COVID-19 in order to prevent disease progression and severity. Regarding the role of bronchodilators, studies have suggested that their combination with IC exerts synergistic therapeutic effects. Objective: To determine the efficacy of inhaled therapy of beclomethasone/formoterol/glycopyrronium (BFG) (100/6/12.5mcg) and/or beclomethasone HFA 250 mcg in preventing the use of healthcare resources in patients ≥ 18 years of age at 28 days compared to usual care. Method: participants will be randomized according to a ratio of 1:1:1 into three groups: (Group 1) Standard of care + BFG two doses 2x/day; (Group 2) standard treatment + beclomethasone HFA two doses 2x/day and (Group 3) standard treatment. After collecting the signed informed consent form, research participants will be treated for 28 days and, after two days, will undergo a spirometry test. Therefore, the total duration of the study for a given participant will be up to 30 days.

Study Overview

• Status: Active, not recruiting
• Conditions: Covid19
• Intervention / Treatment: Drug: inhaled beclametasone; Drug: Inahaled beclomethasone / formoterol / glycopyrronium

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • São Paulo
    • Botucatu, São Paulo, Brazil, 18618687
      • Hospital das Clínicas da Faculdade de Medicina de Botucatu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria: A research participant will be eligible to participate in this study if ALL of the following criteria are met:

1. Adult men or women (≥ 18 years of age)
2. PCR positive SarsCoV-2
3. Symptomatic participants must have at least 1 of the following symptoms in the inclusion: fever or self-reported fever perception in the last 24 hours, headache, sore throat, dry cough, fatigue, chest pain or choking sensation (without associating to respiratory distress), myalgia, anosmia, ageusia or gastrointestinal symptoms with up to 10 days onset.
4. Participants with arterial pulse oximetry (SpO2) saturation ≥ 92% in room air at inclusion.

5. Participants with the following hematological and biochemical laboratory parameters obtained in the period of 7 days before D0:

   • Hemoglobin> 9.0 g / dL-1
   • Absolute Neutrophil Count ≥ 1000 mm-³
   • Platelets ≥ 100,000 mm-3
   • Creatinine clearance ≥ 30 mL / min-1 using the Cockcroft-Gault formula
   • Alkaline phosphatase <10 × upper limit of normal (LSN), AST (TGOS) and ALT (TGPS) <10 × LSN.
   • Laboratory pregnancy test (Negative β-hCG).
6. Participants must understand, sign and date the voluntary informed consent form in writing at the visit prior to any specific protocol procedure.
7. Participants must be able and willing to comply with study visits and procedures, as per the protocol.

Exclusion Criteria:

Research participants who meet any of the following exclusion criteria will be excluded from the study:

1. Participants with moderate or severe acute respiratory failure or needing non-invasive ventilation or oxygen, or with SpO2 <92% or tachypnea (respiratory rate ≥ 30 breaths / minute).
2. Participants with pre-existing, severe and uncontrolled organ failure, which prevents participation in the study by the investigator's judgment (non-relevant cardiac disease)
3. Participant diagnosed with previous asthma using inhaled or oral corticosteroids in the last four weeks.
4. Participant with previous use, in the last ten days of randomization, of inhaled, oral or injectable corticosteroids.
5. Participant with previous diagnosis of chronic obstructive pulmonary disease, even if he is not using any inhaled medication.
6. Pregnant or lactating women.
7. Use of any product under investigation or unregistered within 3 months or within 5 half-lives before baseline, whichever is longer.
8. Hypersensitivity to the drug and / or its excipients.
9. Any condition that, in the investigator's opinion, could compromise the participant's safety or his adherence to the study protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: No intervation; patients receiving standart of care
Active Comparator: Experimental intervation one; patients receiving standart of care + inhaled beclometasone	Drug: inhaled beclametasone; Adding belcamethasone to standard of care for Covid 19 positive patients
Active Comparator: Experimental intervation two; patients receiving standart of care + inhaled beclometasone/ formoterol / glycopyrronium	Drug: Inahaled beclomethasone / formoterol / glycopyrronium; Adding belcametasone/ formoterol / glycopyrronium to standard of care for Covid 19 positive patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients in preventing the use of health resources in patients	28 days after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Airway obstruction	Spirometry	28 days after treatment
Small airway obstruction	computadorized tomography	28 days after treatment

Collaborators and Investigators

• Sponsor: UPECLIN HC FM Botucatu Unesp
• Collaborators: Chiesi Farmaceutici S.p.A.

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2021
• Primary Completion (Actual): October 30, 2021
• Study Completion (Anticipated): May 20, 2022

Study Registration Dates

• First Submitted: June 23, 2021
• First Submitted That Met QC Criteria: June 23, 2021
• First Posted (Actual): June 24, 2021

Study Record Updates

• Last Update Posted (Actual): June 1, 2022
• Last Update Submitted That Met QC Criteria: May 30, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: SARS-CoV-2; corticosteroids; Bronchodilators
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenergic Agonists; Adjuvants, Anesthesia; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Beclomethasone; Glycopyrrolate; Formoterol Fumarate
• Other Study ID Numbers: TRIV001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No