The HOW LONG trial is an international, multicenter, Phase IV randomized clinical trial evaluating the optimal duration of adjunctive systemic corticosteroids in immunocompromised adults with severe Pneumocystis jirovecii pneumonia (PCP) who demonstrate early clinical recovery. Participants who no longer require supplemental oxygen by day 10 of corticosteroid therapy are randomized to discontinue corticosteroids at day 10 (or hospital discharge, if earlier) versus continue corticosteroids for a total of 21 days. The trial assesses whether earlier discontinuation reduces steroid-related complications while maintaining clinical outcomes.
Adjunctive systemic corticosteroids are routinely used in severe PCP to reduce pulmonary inflammation and improve survival, but the recommended 21-day duration is based on limited historical evidence. Prolonged corticosteroid exposure may increase risks including secondary infections, hyperglycemia, gastrointestinal bleeding, and other adverse effects. The HOW LONG trial tests whether stopping corticosteroids earlier, after clinical recovery, improves net clinical outcomes. Eligible adults with proven or probable severe PCP who have recovered to room air (no need for supplemental oxygen) for at least 6 hours by day 10 of corticosteroid therapy are enrolled and randomized centrally 1:1 in the MUHC Research Electronic Data Capture (REDCap) system to (1) discontinuation of corticosteroids at day 10 or hospital discharge or (2) continuation of corticosteroids to a total of 21 days. All participants receive standard antimicrobial therapy for PCP per treating clinicians. Follow-up occurs to day 180. The primary endpoint is a hierarchical composite outcome assessed at day 60, incorporating mortality, relapse of PCP-related hypoxemia, secondary infections, severe metabolic or gastrointestinal complications, and length of hospital stay. Secondary endpoints include individual components of the composite outcome, and tertiary endpoints include quality of life and longer-term outcomes through day 180.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
416
Adjunctive systemiccorticosteroid therapy administered as part of standard treatment for pneumocystis Pneumonia, with duration varying by study arm.
McGill university Health Centre (Royal victoria Hospital and Montreal General Hospital
Montreal, Quebec, Canada
Hierarchical composite clinical outcome
The primary outcome at day 60 will be the hierarchical composite of: 1. death, 2. relapse of PCP-related hypoxemia (e.g., not due to another obviously identified cause like pulmonary embolism, aspiration event, etc.) requiring more than 12 hours of use of ≥2L of oxygen in accordance with guidelines 3. The development of secondary infections requiring systemic antibiotic therapy 4. The development of severe diabetic complications (ketoacidosis, hyperosmolar coma, new initiation of insulin which is continued at discharge) 5. The development of severe GI bleeding (e.g., necessitating unplanned transfusion and/or endoscopy) and; 6. inpatient length of stay (censored at day 60; deaths assigned 60 days).
Time frame: Day 60
Death
Mortality at day 60
Time frame: Day 60
relapse of PCP-related hypoxemia
(Relapse of PCP-related hypoxemia that is not due to another obviously identified cause like pulmonary embolism, aspiration event, etc.) requiring more than 12 hours of use of ≥2L of oxygen in accordance with guidelines
Time frame: Day 60
Secondary infections requiring systemic antibiotic therapy
The development of secondary infections requiring systemic antibiotic therapy
Time frame: Day 60
The development of severe diabetic complications
Severe complications of diabetes include: ketoacidosis, hyperosmolar coma, new initiation of insulin which is continued at discharge
Time frame: Day 60
The development of severe GI bleeding (
Gastrointestinal bleeding necessitating unplanned transfusion and/or endoscopy
Time frame: Day 60
inpatient length of stay (censored at day 60; deaths assigned 60 days).
inpatient length of stay censored at day 60; deaths assigned 60 days.
Time frame: Day 60
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