Steroid Treatment for Severe Acute Respiratory Infection (STAR) Trial

NCT07199192 | Not Yet Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: STRIVE 003
• Study Type: interventional
• Target: 3,000
• Locations: 1 country
• Sites: 1

Brief Summary

Multicenter, parallel-group, randomized clinical trial comparing the administration of systemic corticosteroids at a dose equivalent to 40 mg of prednisolone per day for 7 days vs no corticosteroid administration among adults hospitalized with severe acute respiratory infection and hypoxemia.

Conditions

Hypoxemia; Severe Acute Respiratory Syndrome

Outcome Measures

Primary Outcomes (4)

• 28-day in-hospital mortality

  defined as death from any cause between randomization (Day 0) and 28 days (the end of Study Day 27. Outcome ascertainment ends at hospital discharge.

  Day 28

• Advanced respiratory support

  receipt of extracorporeal membrane oxygenation (ECMO), IMV, noninvasive mechanical ventilation, or high-flow nasal cannula (HFNC) at a rate of ≥30 liters per minute and a fraction of inspired oxygen of ≥0.4. Mechanical ventilation received solely to facilitate the performance of a procedure (e.g., mechanical ventilation for general endotracheal anesthesia limited to the performance of a surgery) will not qualify. Noninvasive mechanical ventilation received solely for the treatment of obstructive sleep apnea or obesity hypoventilation syndrome will not qualify.

  Day 28

• Duration of advanced respiratory support

  calculated as a count of calendar days, beginning with the Study Day on which the participant first received advanced respiratory support and ending with the Study Day on which the participant last received advanced respiratory support during the outcome window. Outcome ascertainment ends at hospital discharge.

  Day 28

• Duration of hospitalization

  calculated as the number of calendar days on which the participant is physically located in a short-term acute care hospital beginning at the time of randomization (Day 0) and ending with the Study Day on which the participant was discharged from the hospital during the outcome window

  Day 28

Study Arms (2)

Corticosteroid Group

EXPERIMENTAL

Participants in the corticosteroid group will receive systemic corticosteroids at a dose equivalent to 40 mg of prednisolone per day for 7 days or until discharge, whichever is sooner. Clinicians will select the systemic corticosteroid medication and the route of administration.

Drug: Corticosteroid

Control Group

NO INTERVENTION

Participants in the no corticosteroid group will not receive systemic corticosteroids for 7 days or until hospital discharge, whichever is sooner, unless (i) they meet prespecified criteria for the administration of systemic corticosteroids (e.g., anaphylaxis) or (ii) their clinicians determine that the administration of systemic corticosteroids is required for the optimal care of the participant for other reasons.

Interventions

Corticosteroid DRUG

systemic corticosteroids at a dose equivalent to 40 mg of prednisolone per day for 7 days or until discharge

Corticosteroid Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Severe acute respiratory infection (SARI), defined as a suspected infection of the respiratory tract that meets each of the following 4 criteria:
• Onset in the last 10 days AND
• Results in hospitalization AND
• At least one symptom or sign of respiratory illness (defined as purulent sputum, new or worsened cough, new or worsened dyspnea, tachypnea with respiratory rate ≥22 breaths per minute, rales, or bronchial breath sounds) AND
• At least one symptom or sign of acute infection (defined as a temperature ≥38°C or ≤36°C, feverishness, chills, altered mental status, a white blood cell count of \>12,000/mm3, \<4,000/mm3, or \>10% immature neutrophils, or imaging findings consistent with acute respiratory infection).
• Hypoxemia, defined as meeting one or more of the following at the time of eligibility assessment:
• An oxygen saturation \<92% in a patient who does not receive chronic supplemental oxygen OR
• Receipt of ≥3 liters per minute of supplemental oxygen or a fraction of inspired oxygen of ≥0.35 in a patient who does not receive chronic supplemental oxygen OR
• Receipt of a flow rate of supplemental oxygen ≥3 liters per minute greater than pre-illness baseline or a fraction of inspired oxygen ≥0.10 greater than pre-illness baseline in a patient who receives chronic supplemental oxygen.

You may not qualify if:

• Hospitalized for \>72 hours
• Primary etiology of hypoxemia is a condition other than respiratory infection
• Known allergy or adverse reaction to systemic corticosteroids
• Known active infection with SARS-CoV-2, known active infection with Pneumocystis jirovecii, or another established indication for systemic corticosteroids
• Known active disseminated or pulmonary infection with Mycobacterium tuberculosis, Aspergillus, Blastomyces, Coccidioides, Cryptococcus, Histoplasma, or Strongyloides species; active systemic infection with herpes simplex virus, varicella zoster virus, or cytomegalovirus; or another established contraindication to systemic corticosteroids
• Prisoner
• Treatment is prioritizing end-of-life symptom management over prolongation of life
• Investigator determines that participation in the trial is not in the patient's best interest
• Receipt of greater than 14 days of systemic corticosteroids at a dose equivalent to greater than 10 mg of prednisolone per day in the 30 days prior to hospital presentation (i.e., chronic corticosteroids)
• Receipt of systemic corticosteroids at a dose equivalent to greater than 30 mg of prednisolone per day on 2 or more calendar days since hospital presentation
• Clinicians determine that the administration of systemic corticosteroids at a dose equivalent to greater than 10 mg of prednisolone per day is required, or is likely to be required in the next 24 hours, for the optimal care of the patient (such as for acute exacerbation of chronic obstructive pulmonary disease, adrenal insufficiency, asthma, continuation of chronic corticosteroid therapy, or severe shock)
• Clinicians determine that the administration of systemic corticosteroids is not consistent with the optimal care of the patient (such as for recent peptic ulcer disease, recent gastrointestinal bleeding, severe burns, severe delirium, severe hyperglycemia or diabetic ketoacidosis, or severe hypertension)
• Patient (or surrogate decision-maker / legally authorized representative) declines to provide informed consent to participate

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• National Institutes of Health (NIH): collaborator
• University of Minnesota: collaborator

Study Sites (1)

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Hypoxia; Severe Acute Respiratory Syndrome

Interventions

Adrenal Cortex Hormones

Condition Hierarchy (Ancestors)

Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Respiratory Tract Infections; Infections; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Matthew W Semler, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

• Jane O'Halloran, MD, PhD

  Washington Univeristy School of Medicine (ID-CRU)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rebecca Schoenecker

CONTACT

612-624-9644; webe0376@umn.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2025
• First Posted: September 30, 2025
• Study Start: March 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: February 19, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)