Treatment of Pneumocystis in COPD (the TOPIC Study)

NCT05418777 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: 2022-102
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

COPD Exacerbation Acute

Keywords

pneumocystitis jirovecii; Chronic Obstructive Pulmonary Disease (COPD); trimethoprim-sulfamethoxazole

Outcome Measures

Primary Outcomes (1)

• Change in the COPD Assessment Test

  Change in total score on the COPD Assessment Test (CAT); the test has a score of 0 (minimum) - 40 (maximum); a lower score means a better outcomes and a higher score means a worse outcome. Negative numbers indicate improvement of condition. Positive numbers indicate worsening of condition.

  Baseline to 3 months

Secondary Outcomes (13)

• Length of Stay for Current AECOPD

  up to 3 months

• Time to Return to Baseline Oxygen for the Current AECOPD

  up to 3 months

• Interval Between Exacerbations of COPD

  up to 3 months

• Interval Between Hospital Admissions

  up to 3 months

• Number of Urgent Care Visits (Total)

  up to 3 months

Study Arms (2)

TMP-SMX

EXPERIMENTAL

Suspension with the equivalent of one DS TMP-SMX by mouth every 12 hours for 10 days

Drug: Trimethoprim Sulfamethoxazole

Placebo

PLACEBO COMPARATOR

Suspension with placebo by mouth every 12 hours for 10 days

Drug: Placebo

Interventions

Trimethoprim Sulfamethoxazole DRUG

Receipt of suspension with the equivalent of one DS TMP-SMX by mouth every 12 hours for 10 days

Also known as: Bactrim, Bactrim DS, Sulfatrim

TMP-SMX

Placebo DRUG

Receipt of suspension with placebo by mouth every 12 hours for 10 days

Also known as: sugar pill

Placebo

Eligibility Criteria

• Age: 40 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Corewell Health East: lead

Study Sites (1)

William Beaumont Hospital

Royal Oak, Michigan, 48073, United States

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Trimethoprim, Sulfamethoxazole Drug Combination; Sugars

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfamethoxazole; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Sulfanilamides; Aniline Compounds; Amines; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Trimethoprim; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Carbohydrates

Limitations and Caveats

Study was terminated due to high screen failure rate leading to low enrollment

Results Point of Contact

• Title: Maureen Cooney, RN Clinical Research Manager
• Organization: William Beaumont Hospitals

maureen.cooney@corewellhealth.org

2485510099

Study Officials

• Matthew Sims, MD, PhD

  Corewell Health East

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director Infectious Disease Research, Beaumont Health; Professor of Internal Medicine and Foundational Medical Studies, OUWB School of Medicine

Study Record Dates

• First Submitted: June 9, 2022
• First Posted: June 14, 2022
• Study Start: September 28, 2022
• Primary Completion: December 19, 2022
• Study Completion: December 19, 2022
• Last Updated: November 29, 2023
• Results First Posted: November 29, 2023

Record last verified: 2023-11

Locations

US (1)