Treatment of Pneumocystitis in COPD (the TOPIC Study)

• Status: Recruiting
• Trial end date: 2023-08-01
• Target enrollment: 0
• Participant gender: All

Summary

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease associated with chronic inflammation in the airways and lung, resulting in significant morbidity and mortality worldwide. Smoking is the primary risk factor for development of COPD and progression of the disease is associated with acute exacerbations of COPD (AECOPD) that can be triggered by acute bacterial or viral airway infections or can occur independently of infection. AECOPD can lead to hospitalization, progression of the disease, and mortality. COPD affects an estimated 11.7% of the world population and was the third leading cause of death worldwide in 2019.

This study is a randomized, double-blinded and placebo controlled study to determine if treating PJ in AECOPD with confirmed PJ colonization has a beneficial clinical impact. As a secondary goal of the study, it will be determined if TMP-SMX can decolonize these patients and if the decolonization is durable for at least 3 months.

The causes of progression of COPD, especially in the absence of continued tobacco use, are incompletely understood and a significant area of need. One proposed trigger for progression and increased AECOPD is colonization (presence of the organism without an actual infection) with Pneumocystis jirovecii (PJ), a fungal pathogen best known for causing pneumonia in patients with HIV or other forms of immunosuppression. It has been found to be more prevalent in those with severe COPD, particularly during AECOPD, but as a colonizer, not a cause of acute pneumonia. Several studies have linked PJ with progression of COPD, showing that PJ perpetuates an inflammatory and lung remodeling response, contributing to development of airway obstruction, emphysema and accelerating the disease course.

The aim of this study is to add trimethoprim-sulfamethoxazole (TMP-SMX) to standard of care treatment of AECOPD in patients who are colonized with PJ will improve the clinical outcome for the patient. This study is a pilot which will serve as proof of concept that screening for PJ in the AECOPD population and treating it with the commonly available, safe, and inexpensive antibiotic TMP-SMX will be an effective strategy.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: William Beaumont Hospitals
• Treatments: Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Criteria

Inclusion Criteria:

• Carries the diagnosis of COPD and admitted for and admitted with AECOPD to Beaumont, Royal Oak (AECOPD requires increased cough, increased sputum production, and shortness of breath +/- increased oxygen needs from baseline)

• Able to produce a sputum sample

• Men or women, age ≥ 40 and < 90

• Previously enrolled in the EPIC Study and positive for Pneumocystis jirovecii detected in their sputum

• Currently treated with steroids

• Kidney function not severely impaired (CrCl ≥ 60)

• AST and ALT ≤5x upper limit of normal

• Willing and able to consent to the study

Exclusion Criteria:

• Current diagnosis of pneumonia or COVID-19

• Allergy or hypersensitivity to trimethoprim-sulfamethoxazole

• Current ICU admission or mechanical ventilation

• Active cancer or chemotherapy (except non-melanoma skin cancer)

• Other potentially confounding pulmonary diagnosis

• HIV, leukopenia, neutropenia, or other immunosuppressive condition or current use of immunosuppressive medications

• Presence of gastrointestinal tract abnormalities that would prevent absorption of medications

• Patients with concomitant infection requiring antibiotics active against Pneumocystis jirovecii

• Concomitant use of coumadin, phenytoin, pioglitazone, repaglinide, rosiglitazone, glipizide or glyburide

• Megaloblastic anemia due to folate deficiency

• Pregnancy

• Life expectancy less than 3 months