Efficacy and Safety of Prophylactic Treatment for Pneumocystis Jirovecii Pneumonia in Patients With Autoimmune Inflammatory Rheumatic Disease

Efficacy and Safety of Prophylactic Treatment for Pneumocystis Jirovecii Pneumonia (PJP) in Patients With Autoimmune Inflammatory Rheumatic Disease (AIIRD)

This is an open-labeled, prospective clinical study aims at collecting and analyzing baseline characteristics of autoimmune inflammatory rheumatic disease (AIIRD) patients receiving sulfanilamide for preventive purposes, as well as subsequent follow-up data, in order to assess the efficacy and safety of the medication. Additionally, through a stratified analysis of risk factors, the investigators aim to identify the AIIRD population that would benefit most from preventive medication based on a favorable benefit-risk ratio.

Study Overview

• Status: Recruiting
• Conditions: Autoimmune Diseases; Pneumonia, Pneumocystis; Prevention; Connective Tissue Disease; Autoimmune Inflammatory Rheumatic Disease
• Intervention / Treatment: Drug: Trimethoprim/Sulfamethoxazole

• Study Type: Interventional
• Enrollment (Estimated): 800
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Lingli Dong; Phone Number: 02783665519; Email: tjhdongll@163.com
• Study Contact Backup: Name: Shaozhe Cai; Phone Number: 02783665518; Email: 540361903@qq.com

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 43003
      • Recruiting
      • Tongji Hospital
      • Contact: Dong Lingli, MD; Phone Number: +862783665519; Email: tjhdongll@163.com
      • Contact: Cai Shaozhe, MD; Phone Number: +862783665519; Email: 540361903@qq.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. The patient was diagnosed with AIIRD according to the International Classification of Diseases and had received steroids or immunosuppressive therapy;
2. The patient had not received standard PJP treatment before enrollment, including the first-line treatment drug TMP/SMZ, or other second-line treatment drugs (including Pentamidine, Atorvastatin, Caspofungin, etc.);
3. The patient was at least 18 years old at the time of enrollment;

Exclusion Criteria:

1. Serious health problems or diseases, including (but not limited to) the following: severe liver damage (ALT, AST elevated above normal value by more than 5 times), severe renal insufficiency (GFR < 30mL/min or Scr > 445umol/L), severe myelosuppression (Hb < 65g/L, PLT < 25×10^9/L or neutrophils < 0.5×10^9/L);
2. Screening test indicates infection with human immunodeficiency virus (HIV), history of lymphomatous hyperplasia of the lymphatic tissue or any malignant tumor of any organ system within the past 5 years, or history of organ transplantation;
3. Participants with a history of allergy to sulfonamide drugs, megaloblastic anemia due to folate deficiency;
4. Pregnant and lactating women;
5. Any medical or psychological condition that the investigator believes would interfere with the participant's ability to comply with the protocol or complete the study;
6. Patients who refuse to comply with the requirements of this study and complete the study;
7. Any other situation that the investigator considers unsuitable for participation in the study (for reasons including but not limited to management reasons).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TMP/SMX (with PJP high risk); AIIRD patients who have PJP high risk and receive prophylactic Trimethoprim/ Sulfamethoxazole (TMP/SMZ) treatment; Drug intervention: Patients receive Trimethoprim/Sulfamethoxazole (TMP/SMX) 480 mg p.o. every day as PJP Prophylaxis.	Drug: Trimethoprim/Sulfamethoxazole; Patients received Trimethoprim/Sulfamethoxazole (TMP/SMX) 480 mg p.o. every day as PJP Prophylaxis; Treatment duration: at least 28 days, adjusted by the clinician based on the severity of the patient's condition, the patient's tolerance to the drug and treatment willingness).; Other Names: TMP/SMX
No Intervention: no TMP/SMX (with PJP high risk); AIIRD patients who have PJP high risk and do not receive prophylactic Trimethoprim/ Sulfamethoxazole (TMP/SMZ) treatment.
Experimental: TMP/SMX (with PJP low-risk); AIIRD patients who have PJP low risk and receive prophylactic Trimethoprim/ Sulfamethoxazole (TMP/SMZ) treatment; Drug intervention: Patients receive Trimethoprim/Sulfamethoxazole (TMP/SMX) 480 mg p.o. every day as PJP Prophylaxis.	Drug: Trimethoprim/Sulfamethoxazole; Patients received Trimethoprim/Sulfamethoxazole (TMP/SMX) 480 mg p.o. every day as PJP Prophylaxis; Treatment duration: at least 28 days, adjusted by the clinician based on the severity of the patient's condition, the patient's tolerance to the drug and treatment willingness).; Other Names: TMP/SMX
No Intervention: no TMP/SMX (with PJP low-risk); AIIRD patients who have PJP low risk and do not receive prophylactic Trimethoprim/ Sulfamethoxazole (TMP/SMZ) treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with PJP infection	Defined as documentation/diagnosis of Pneumocystis from a properly obtained specimen (induced sputum, bronchoalveolar lavage, or biopsy) in a patient with clinical manifestations compatible with PJP.	6 months, 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TMP/SMZ related adverse drug reactions	Symptoms and signs that may be related to adverse drug reactions during treatment (such as nausea, vomiting, anorexia, jaundice, rashes and hives, and shock); incidence, duration and severity of adverse events	6 months, 12 months
PJP-related mortality	PJP-related mortality at the end of month 6.	6 months, 12 months
All cause mortality	All cause mortality	6 months, 12 months

Collaborators and Investigators

• Sponsor: Tongji Hospital
• Investigators: Principal Investigator: Lingli Dong, Tongji Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2024
• Primary Completion (Estimated): July 20, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: July 6, 2024
• First Submitted That Met QC Criteria: July 6, 2024
• First Posted (Actual): July 12, 2024

Study Record Updates

• Last Update Posted (Actual): October 1, 2024
• Last Update Submitted That Met QC Criteria: September 27, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Musculoskeletal Diseases; Bacterial Infections and Mycoses; Mycoses; Lung Diseases, Fungal; Pneumocystis Infections; Pneumonia; Rheumatic Diseases; Collagen Diseases; Connective Tissue Diseases; Autoimmune Diseases; Pneumonia, Pneumocystis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Folic Acid Antagonists; Anti-Dyskinesia Agents; Anti-Infective Agents, Urinary; Cytochrome P-450 CYP2C8 Inhibitors; Trimethoprim; Sulfamethoxazole
• Other Study ID Numbers: TJ-IRB20231250

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
• product manufactured in and exported from the U.S.: Yes