Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT05418777 |
| Other study ID # |
2022-102 |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
Phase 1/Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
September 28, 2022 |
| Est. completion date |
December 19, 2022 |
Study information
| Verified date |
November 2023 |
| Source |
William Beaumont Hospitals |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
Description:
The current standard of care for detection of PJ has significant limitations in COPD
patients. There is no reliable in vitro culture system and traditional detection methods are
based on histochemical staining with direct fluorescent antibodies (DFA) that target the cyst
form of the organism isolated from bronchoalveolar lavage (BAL) fluid. BAL is an invasive
diagnostic procedure that often cannot be performed safely in patients with AECOPD due to
associated risk of worsening respiratory failure and intubation. In non-HIV patients, PJ is
at a lower bioburden and generally exists in the vegetative form rather than the cyst form.
The lower PJ cyst burden leads to a lower sensitivity of DFA (20%) which specifically targets
the cyst form. This in turn leads to difficulty in identifying PJ in the non-HIV population
including transplant and COPD patients. This has led to a lack of clinical trials for
potential therapeutic interventions targeting PJ to treat AECOPD or to prevent progression of
COPD. A novel method of non-invasive sample collection of sputum analysis with the Unyvero
system which is a novel nucleic acid amplification testing (NAAT) based assay demonstrated to
have high sensitivity for PJ is being used to determine prevalence of PJ in the AECOPD
population. The ability to routinely identify the subgroup of patients colonized with PJ
among the hospitalized patients with AECOPD is a necessary step toward selection of the most
appropriate potentially treatable patients to include in this pilot study designed to treat
AECOPD.
Trimethoprim-sulfamethoxazole (TMP-SMX) is the standard of care for treating PJ pneumonia in
HIV patients, and has been shown in prior studies to have high clinical cure rates. Our
intervention is adding TMP-SMX to the treatment regimen for patients hospitalized with AECOPD
and colonized with PJ. The goal of this study is 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.
Participants will be randomized in a 1:1 ratio to one of two groups. Group #1 will receive a
suspension with the equivalent of one double strength (DS) TMP-SMX by mouth every 12 hours.
Group #2 will received a suspension with placebo by mouth every 12 hours. If the participant
is discharged prior to completing the 10-day course of the medication, they will be sent home
with the remaining days of study medication and a medication diary which will be collected at
the end of therapy visit. When a patient with PJ pneumonia is hypoxic, the treatment of the
PJ in addition to TMP-SMX includes steroids.
Upon consent patients will be given the COPD Assessment Test (CAT)
(https://www.mdcalc.com/copd-assessment-test-cat), a validated scoring system used in COPD
patients to assess progression, functional status, and effectiveness of pulmonary
rehabilitation. Participants will be monitored daily while in the hospital for highest oxygen
need, need for non-invasive or invasive mechanical ventilation, and adverse events, daily
monitoring will be carried out by the nurse coordinator. Medications used for the treatment
of COPD and antibiotics used will be collected retrospectively for each patient. If the
patient remains hospitalized at end of therapy, 30 days, or 90 days then follow up will occur
in the hospital. Otherwise, the patient will be asked to come to the Infectious Diseases
Clinical Research Office for follow up visits at end of therapy (+0-3 days to allow for
schedule issues and end of therapy falling on a weekend), 30 days +/-5 days, and 90 days +/-
10 days. A $30 stipend will be paid to the participants after each follow up visit. At the
end of treatment visit, the medication diary will be collected. At each follow up visit, the
nurse coordinator will review the patient's need for oxygen, their medications for the
treatment of COPD, any need to see a physician or go to an urgent care or an emergency room
for COPD, and any admission to the hospital for COPD. The CAT will be administered at each
follow up visit. An expectorated sputum sample will be collected at each follow up visit
which will be transported to the Infectious Diseases Research Laboratory for analysis; sputum
samples will be processed and analyzed with the Unyvero system for presence of PJ by
polymerase chain reaction (PCR).
