Interleukin 6-guided Antibiotic Prescriptions in AECOPD Inpatients

Interleukin 6-guided Antibiotic Prescriptions in AECOPD Inpatients: a Multicenter Randomized Controlled Trial

In this multicenter, prospective, randomized controlled study, we aimed to figure out, compared with the global chronic obstructive pulmonary disease initiative (GOLD) guideline -guided antibiotic therapy, whether Interleukin 6 (IL6)-guided antibiotic therapy for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) can lead to a reduction in the use of antibiotics without increasing the rate of treatment failure.

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Obstructive Pulmonary Disease, COPD
• Intervention / Treatment: Drug: Interleukin 6-guided antibiotic therapy; Drug: GOLD-guided antibiotic therapy

Detailed Description

Acute exacerbation is the first leading cause of hospitalization and mortality among patients with COPD. Infection of bacteria has been detected in 49.59% of patients with AECOPD. Antibiotic prescriptions for AECOPD patients are usually based on GOLD guideline. However, the newest study reported that more than 85% of AECOPD inpatients received antibiotic prescription in the United States, Europe and China. Not all patients will equally experience benefit from antibiotics. Interleukin 6 (IL6) was determined as a reliable clinical biomarker in guiding antimicrobial use. It remains unclear whether IL6-guided antibiotic therapy is safe and effective for hospitalized patients with AECOPD.

The study will recruit 440 AECOPD inpatients from at least six hospitals based in China. Eligible participants will be assigned to receive either IL6-guided antibiotic therapy or GOLD-guided antibiotic therapy in 1:1 ratio randomly. The hypothesis for this study is that IL-6 guided antibiotic therapy will reduce the rate of antibiotic prescriptions for AECOPD without increasing the rate of treatment failure, compared with the group treated with GOLD-guided antibiotic therapy.

• Study Type: Interventional
• Enrollment (Estimated): 440
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: 依婷 Cao; Phone Number: +86-0574-87089878; Email: liyiting1022@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. AECOPD patients admitted to hospitals
2. The exacerbation has lasted for at least 24 hours but equal to or less than 21 days
3. ≥40 years of age but no more than 80 years old
4. With at least 10 pack-year history of smoking
5. Able to provide written informed consent and ensure the completion of the trial

Exclusion Criteria:

1. Axillary temperature≥38°C
2. Acute pneumonia identified by X-Ray or CT of the chest
3. Severe respiratory failure requiring admittance to ICU
4. Comorbidities require antibiotic therapy (i.e. infection at another site, systematic infection, active chronic inflammatory condition, specific viral infection)
5. Immunosuppression status (i.e., patients with HIV infection, with malignant tumor of blood system, receiving chemotherapy)
6. Concurrent diseases requiring corticosteroids (equivalent to 60mg prednisone/day or more than 30 days)
7. Antibiotic use in the previous four weeks
8. Current tracheotomy status
9. Bronchiectasis of origin other than COPD
10. Invasive mechanical ventilation
11. Patients diagnosed malignant tumors
12. Pregnant or lactating women, or women of childbearing age not using an acceptable method of contraception.
13. Newly diagnosed pulmonary embolism
14. Participation in another clinical trial

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Interleukin 6-guided antibiotic therapy (Interleukin-6 group); After randomization, baseline blood samples will be drawn within 2 hours. Prescribing clinician are able to access the results of the IL-6 through the internal network of the hospital. Participants' antibiotic prescription decisions will made according to the results. The detailed recommendations are as follows: if Interleukin-6<10 pg/ml，strongly discouraged；if Interleukin-6 (10-30 pg/ml) and no sputum purulence, discouraged; if Interleukin-6 (10-30 pg/ml) and sputum purulence, Recommended; Interleukin-6>30 pg /ml, Strongly recommended.	Drug: Interleukin 6-guided antibiotic therapy; In Interleukin-6 group, antibiotic prescription decisions will made according to the results of IL-6.
Active Comparator: GOLD-guided antibiotic therapy (GOLD group); After randomization, baseline blood samples will also need to be drawn within 2 hours. Prescribing clinician are able to access all results through the internal network of the hospital. Participants' antibiotic prescription decisions will made according to the recommendations of GOLD guideline. The guideline recommends antibiotic therapy for the following patients: those with COPD exacerbations presenting with all three cardinal symptoms (increased dyspnea, sputum volume, and sputum purulence); those with two of the cardinal symptoms, provided that increased purulence of sputum is one of them; or those who need mechanical ventilation (either invasive or noninvasive).	Drug: GOLD-guided antibiotic therapy; In guideline group, antibiotic prescription decisions will made according to the recommendations of GOLD guideline.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of antibiotic use	Ratio of AECOPD patients given antibiotics	During the 30-day period after randomization
Proportion of successful treatments	Treatment success is achieved when there is a cure (full resolution of all symptoms and signs of the exacerbation) or improvement (diminishment or resolution of symptoms and signs from the exacerbation, with no additional symptoms or signs).	During the 30-day period after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of antibiotic use	Ratio of AECOPD patients given antibiotics	During the first day period after randomization
Antibiotic utilization in the hospital	Duration of antibiotic consumption for AECOPD and the percentage of patients treated with antibiotics for AECOPD from randomization to hospital discharge	Between randomization and discharge, limited to 30 days
Duration of hospitalization	Total days of hospitalization until study completion, averaging 30 days	Between randomization and discharge, limited to 30 days
Frequency of subsequent exacerbations	Ratio of patients who develop a subsequent acute exacerbation following recovery	During the 30-day period after randomization
Incidence of hospital readmission	Ratio of patients rehospitalized for AECOPD following discharge	Between the discharge date and 30 days post-randomization
All-cause mortality	Death due to any cause	During the 30-day period after randomization
Frequency of ICU admissions	Ratio of patients admitted to the intensive care unit	During the 30-day period after randomization
noninvasive mechanical ventilation	Ratio of patients provided with non-invasive mechanical ventilation	During the 30-day period after randomization
Change in COPD assessment test	The variation from the baseline at hospital admission to 30 days after randomization	From the initial hospital admission baseline to 30 days after randomization
Change in St. George's Respiratory Questionnaire	The variation from the baseline at hospital admission to 30 days after randomization	From the initial hospital admission baseline to 30 days after randomization
Change in modified Medical Research Council (mMRC) score	The variation from the baseline at hospital admission to 30 days after randomization	From the initial hospital admission baseline to 30 days after randomization
Change in Hospital Anxiety and Depression Scale	The variation from the baseline at hospital admission to 30 days after randomization	From the initial hospital admission baseline to 30 days after randomization

Collaborators and Investigators

• Sponsor: Ningbo No. 1 Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): September 20, 2024
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2026

Study Registration Dates

• First Submitted: September 21, 2024
• First Submitted That Met QC Criteria: September 21, 2024
• First Posted (Actual): September 25, 2024

Study Record Updates

• Last Update Posted (Actual): September 25, 2024
• Last Update Submitted That Met QC Criteria: September 21, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Interleukin 6; antibiotic therapy; Aecopd
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Chronic Disease; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Anti-Infective Agents; Antitubercular Agents; Anti-Bacterial Agents; Antibiotics, Antitubercular
• Other Study ID Numbers: 2024-R046-02

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