Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
Chronic Obstructive Pulmonary Disease, Pneumocystis jirovecii, Trimethoprim-Sulfamethoxazole
Brief summary
Previous researches have found the common colonization of Pneumocystis jirovecii (Pj) in the airways of people with chronic obstructive pulmonary disease (COPD). And this colonization may exacerbate airway inflammation and increase the frequency of acute exacerbation in people with COPD. The goal of this clinical trial is to study if "decolonization treatment" (that is, removing these colonizing Pj) works to improve the prognosis of COPD colonized by Pj in adults. The main question it aims to answer is: * Does the Trimethoprim-Sulfamethoxazole (TMP-SMX, an antibiotics) decolonization treatment reduce the frequency of acute exacerbation in participants with COPD colonized by Pj who have a high risk of acute exacerbation. Researchers will compare TMP-SMX to a placebo (a look-alike substance that contains no drug) to see if TMP-SMX works to reduce the frequency of acute exacerbation of COPD. Participants will: * Take drug TMP-SMX or a placebo 2 tablet every day for 4 weeks. * Visit the clinic after 2 weeks, 1 month, 3 months, 6 months and 12 months for survey questions, checkups and tests. * Keep a diary of their symptoms and the number of times they experience acute exacerbations
Interventions
Receipt of tablet with the equivalent of one double-strength (DS) TMP-SMX（TMP 160mg + SMZ 800mg） per day by mouth for 4 weeks
DRUGPlacebo
Receipt of tablet with placebo by mouth every day for 4 weeks
Sponsors
Second Affiliated Hospital, School of Medicine, Zhejiang University
First Affiliated Hospital of Zhejiang University
Zhejiang Rongjun Hospital
Zhejiang Quhua Hospital
West China Hospital
Shanghai Pulmonary Hospital, Shanghai, China
Second Affiliated Hospital of Nanchang University
Shanghai Tongji Hospital, Tongji University School of Medicine
Huzhou Central Hospital
Shaoxing People's Hospital
Affiliated Hospital of Jiaxing University
Red Cross Hospital, Hangzhou, China
Taizhou Hospital
Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University
The First Affiliated Hospital of Guangzhou Medical University
First Affiliated Hospital of Wenzhou Medical University
Zhejiang Hospital
Sir Run Run Shaw Hospital
Lishui hospital of Zhejiang University
Tongji Hospital
The Sixth Affiliated Hospital of Wenzhou Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 40 and above，male or female； * COPD who meet the diagnostic criteria of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2026 ( post-bronchodilator FEV1/forced vital capacity \[FVC\] ratio \< 0.7 and post-bronchodilator FEV1% predicted ≥ 30%), and have documented history of high exacerbation risk (Group E, defined as exacerbation history of ≥ 1 moderate or severe acute exacerbation within 12 months prior to inclusion)； * Background triple therapy (ICS + LABA + LAMA) for 3 months prior to randomization with a stable dose of medication for ≥1 month prior to inclusion; Double therapy (LABA + LAMA) allowed if ICS is contraindicated； * PCR detection of Pneumocystis jirovecii in induced sputum is positive； * Informed consent
Exclusion criteria
* Allergic to TMP, SMX or sulfonamide drugs； * There are pneumonia or other infections that require long-term use of antibacterial drugs (such as tuberculosis, NTM, other fungi, etc.)； * Having used antibiotics within the previous 4 weeks prior to screening； * Experience of AECOPD events within the previous 4 weeks prior to screening; * Having a definite immunodeficiency disorder or receiving immunosuppressive therapy (such as HIV, agranulocytosis, solid organ or hematopoietic stem cell transplantation, malignant tumors, using long-term high-dose hormones \> 20mg/day prednisone equivalent for more than 4 weeks)； * Severe liver and kidney dysfunction (ALT/AST \> 3 times the upper limit of normal value, eGFR \< 60 mL/min/1.73m²)； * Pregnant, lactating women or those planning to become pregnant; * Folic acid deficiency-induced microcytic anemia; * Currently using coumarin, phenytoin, pioglitazone, repaglinide, rosiglitazone, glipizide or glibenclamide; * Currently participating in other interventional clinical studies；
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Annualized rate of moderate or severe acute exacerbations of chronic obstructive pulmonary disease (COPD) over one year | Baseline (Day 1) to 12 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The clearance rate of TMP-SMX in eliminating Pneumocystis jirovecii in the lower respiratory tract | 1month | — |
| The duration of clearance of Pneumocystis jirovecii in the lower respiratory tract | 3 months，12 months | — |
| Change from baseline in COPD Assessment Test (CAT) total score | 1month，3 months，6 months and 12 months | 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. |
| Change from baseline in modified Medical Research Council dyspnea scale (mMRC) | 1month，3 months，6 months and 12 months | The mMRC scale consists of 5 grades (0-4), based on how much breathlessness limits physical activity. Higher mMRC scores mean a worse outcome. |
| All-cause mortality rate | Baseline to 12 months | — |
| Airway microbiota analysis | Baseline to 1month and 12 months | The microbiome of qualified sputum will be measurable by metagenomic next-generation sequencing (mNGS) technologies. Its characteristic parameters include the alpha diversity and beta diversity of the microbiome. |
| Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Baseline to 3 months，6 months and 12 months | — |
| Incidence rate of adverse events | 2 weeks and 1 month | — |
Countries
China
Contacts
CONTACTHua Zhou, Doctor
Outcome results
None listed