Study on the Impact of Decolonization Treatment of Pneumocystis Jirovecii on the Frequency of Acute Exacerbation in COPD

A Multicenter, Prospective, Double-blind, Randomized Controlled Study on the Impact of Decolonization Treatment on the Frequency of Acute Exacerbation in Patients With Chronic Obstructive Pulmonary Disease Colonized With Pneumocystis Jirovecii

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

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Obstructive Pulmonary Disease (COPD)
• Intervention / Treatment: Drug: Trimethoprim-Sulfamethoxazole (TMP-SMX); Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 630
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hua Zhou, Doctor; Phone Number: +86 571 8723 6876; Email: zhouhua1@zju.edu.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • The First Affiliated Hospital of Guangzhou Medical University
      • Contact: Zhengtu Li
  • Hubei
    • Wuhan, Hubei, China
      • Tongji Hospital
      • Contact: Yuanzhou He
  • Jiangxi
    • Nanchang, Jiangxi, China
      • Second Affiliated Hospital of Nanchang University
      • Contact: Xinyi Zhang
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China
      • Shanghai Pulmonary Hospital, Shanghai, China
      • Contact: Shuyi Gu
    • Shanghai, Shanghai Municipality, China
      • Shanghai Tongji Hospital, Tongji University School of Medicine
      • Contact: Yingzhou Xie
  • Sichuan
    • Chengdu, Sichuan, China
      • West China Hospital
      • Contact: Chengdi Wang
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Sir Run Run Shaw Hospital
      • Contact: Hequan Li
    • Hangzhou, Zhejiang, China
      • Zhejiang Hospital
      • Contact: Jian Ye
    • Hangzhou, Zhejiang, China
      • First Affiliated Hospital of Zhejiang University
      • Contact: Yinan Yao; Email: yaoyinan@zju.edu.cn
    • Hangzhou, Zhejiang, China
      • Red Cross Hospital, Hangzhou, China
      • Contact: Chuhui Ru
    • Huzhou, Zhejiang, China
      • Huzhou Central Hospital
      • Contact: Bin Wang
    • Jiaxing, Zhejiang, China
      • Affiliated Hospital of Jiaxing University
      • Contact: Wenyu Chen
    • Jiaxing, Zhejiang, China
      • Zhejiang Rongjun Hospital
      • Contact: Lixin Wu
    • Lishui, Zhejiang, China
      • Lishui hospital of Zhejiang University
      • Contact: Youyi Du
    • Lishui, Zhejiang, China
      • The Sixth Affiliated Hospital of Wenzhou Medical University
      • Contact: Jinwei Huang
    • Quzhou, Zhejiang, China
      • Zhejiang Quhua Hospital
      • Contact: Kai Fang
    • Shaoxing, Zhejiang, China
      • Shaoxing People's Hospital
      • Contact: Xing Chen
    • Taizhou, Zhejiang, China
      • Taizhou Hospital
      • Contact: Junfei Zhu
    • Taizhou, Zhejiang, China
      • Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University
      • Contact: Xiaomai Wu
    • Wenzhou, Zhejiang, China
      • First Affiliated Hospital of Wenzhou Medical University
      • Contact: Yuping Li

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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；

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TMP-SMX; Tablet with the equivalent of one DS TMP-SMX per day by mouth for 4 weeks	Drug: Trimethoprim-Sulfamethoxazole (TMP-SMX); Receipt of tablet with the equivalent of one double-strength (DS) TMP-SMX（TMP 160mg + SMZ 800mg） per day by mouth for 4 weeks; Other Names: Bactrim; Sulfatrim
Placebo Comparator: placebo; Tablet with placebo by mouth every day for 4 weeks	Drug: Placebo; Receipt of tablet with placebo by mouth every day for 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	1month，3 months，6 months and 12 months
Change from baseline in modified Medical Research Council dyspnea scale (mMRC)	The mMRC scale consists of 5 grades (0-4), based on how much breathlessness limits physical activity. Higher mMRC scores mean a worse outcome.	1month，3 months，6 months and 12 months
All-cause mortality rate		Baseline to 12 months
Airway microbiota analysis	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.	Baseline to 1month and 12 months
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

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Collaborators: West China Hospital; Tongji Hospital; First Affiliated Hospital of Zhejiang University; The First Affiliated Hospital of Guangzhou Medical University; Shanghai Pulmonary Hospital, Shanghai, China; Sir Run Run Shaw Hospital; Red Cross Hospital, Hangzhou, China; First Affiliated Hospital of Wenzhou Medical University; Shaoxing People's Hospital; Shanghai Tongji Hospital, Tongji University School of Medicine; Second Affiliated Hospital of Nanchang University; Taizhou Hospital; Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University; Lishui hospital of Zhejiang University; The Sixth Affiliated Hospital of Wenzhou Medical University; Zhejiang Quhua Hospital; Zhejiang Hospital; Affiliated Hospital of Jiaxing University; Zhejiang Rongjun Hospital; Huzhou Central Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): May 1, 2029

Study Registration Dates

• First Submitted: June 15, 2026
• First Submitted That Met QC Criteria: June 18, 2026
• First Posted (Actual): June 24, 2026

Study Record Updates

• Last Update Posted (Actual): June 24, 2026
• Last Update Submitted That Met QC Criteria: June 18, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Chronic Obstructive Pulmonary Disease; Trimethoprim-Sulfamethoxazole; Pneumocystis jirovecii
• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pathological Conditions, Signs and Symptoms; Pulmonary Disease, Chronic Obstructive; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pharmaceutical Preparations; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Amides; Aniline Compounds; Amines; Pyrimidines; Benzene Derivatives; Drug Combinations; Sulfamethoxazole; Benzenesulfonamides; Sulfonamides; Sulfanilamides; Sulfones; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination
• Other Study ID Numbers: 2026-0378

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No