Prevention of Acute Exacerbation in Subjects With COPD by Bacterial Decolonization in Lower Respiratory Tract

NCT03449459 | Completed Early Phase 1

• 2 other identifiers: B2017-197R2017YFC1309303
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 3

Brief Summary

The colonization of potential pathogenic bacteria in lower respiratory tract is thought to be accountable for acute exacerbation in subjects with moderate to severe COPD. However, there is no accepted therapy for patients with COPD to remove the colonized bacteria in lower respiratory tract. Therefore, we plan to perform a multi-center, randomized, controlled trial to study the efficacy and safety of oral probiotics, aerosol inhaled amikacin or combined vaccination to decolonize bacteria in lower respiratory tract and prevent acute exacerbation of COPD.

Conditions

Chronic Obstructive Pulmonary Disease (COPD)

Keywords

chronic obstructive pulmonary disease; aerosol inhaled amikacin; oral probiotics; combined influenza and pneumococcal vaccine inoculation; bacterial decolonization in lower respiratory tract

Outcome Measures

Primary Outcomes (1)

• Time to the first COPD exacerbation

  COPD exacerbation refers to deterioration of patients' daily symptoms requiring treatment with antibiotics or systemic glucocorticoid therapy. First COPD exacerbations starting between first dose and one day after last follow-up are included.

  15 months

Secondary Outcomes (10)

• Colonization of potential pathogenic bacteria in induced sputum

  Baseline, 3 months

• Microbiome in induced sputum

  Baseline, 3 months

• Forced Expiratory Volume in 1 Second

  Baseline, 3 months, 15 months

• COPD Assessment Test(CAT) Score

  Baseline, 3 months, 6 months, 9 months, 12 months, 15 months

• modified Medical Research Council(mMRC) scale

  Baseline, 3 months, 6 months, 9 months, 12 months, 15 months

Study Arms (4)

oral probiotics

EXPERIMENTAL

Dietary Supplement: oral probiotics

aerosol inhaled amikacin

EXPERIMENTAL

Drug: aerosol inhaled amikacin

combined vaccination

EXPERIMENTAL

Biological: combined vaccination

conventional therapy (blank control)

NO INTERVENTION

According to the subjects' personal characteristics and guidance of The Global Initiative for Chronic Obstructive Lung Disease(GOLD) 2017, the doctor in charge prescribes appropriate medication, including but not limited to bronchodilators, inhaled glucocorticoids and long term oxygen therapy.

Interventions

oral probiotics DIETARY_SUPPLEMENT

Culturelle™ DIGESTIVE HEALTH 30 CT(VCAP)(10 Billion Claim) which consists of 100% Lactobacillus rhamnosus GG, 1 tablet, q.d., for 3 months. Subjects will take conventional therapy at the same time.

oral probiotics

aerosol inhaled amikacin DRUG

0.4g Amikacin sulfate injection + 5ml saline, aerosol inhalation, b.i.d., 5-7 days per month, for 3 months. In order to observe and cope with adverse events timely, subjects will be admitted to the ward during the course of medication. Subjects will take conventional therapy at the same time.

aerosol inhaled amikacin

combined vaccination BIOLOGICAL

Influenza Vaccine recommended by World Health Organization(WHO) in that year and imported 23-Valent Pneumococcal Polysaccharide Vaccine approved by China Food and Drug Administration(CFDA) are vaccinated at different body sites by professional nurses. The interval between two vaccinations is 3-5 days to avoid the overlap of adverse events. Subjects will take conventional therapy at the same time.

combined vaccination

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent must be obtained before any assessment is performed
• Male or female adults aged 18-65 years
• Diagnosed with COPD according to GOLD 2016 (The ratio of post-bronchodilator forced expiratory volume in 1 second (FEV1) to force vital capacity (FVC)\<0.70 with the use of salbutamol 400ug)
• Moderate to very severe airflow limitation (post-bronchodilator FEV1 \< 80% of the predicted normal value)
• A documented history of at least 2 COPD exacerbation in the previous 12 months that required treatment with systemic glucocorticoids and/or antibiotics, or at least 1 exacerbation in the previous 12 months that requires hospitalization.
• In the stable stage of COPD

You may not qualify if:

• Patients who have clinically significant and chronic hepatic, renal, cardiovascular and gastrointestinal abnormalities or malignant tumor (except for lung cancer) which could interfere with the assessment of the efficacy and safety of the study treatment
• Patients who are in critical conditions
• Patients who have had a COPD exacerbation that required treatment with antibiotics and/or systemic corticosteroids or an acute exacerbation of any other diseases in the 4 weeks prior to screening
• Patients with concomitant pulmonary disease (including but not limited to bronchiectasis, interstitial lung disease, asthma)
• Patients who are highly likely to be lost during the 3-month treatment and the 1-year follow up
• Pregnant or nursing (lactating) women
• Patients who have been vaccinated against influenza in the current year, or against Streptococcus pneumoniae within five years, or have vaccination contraindications
• Patients who are allergic to amikacin or other aminoglycosides
• Patients who have participated in any interventional clinical trials in the three months prior to screening
• Patients with mental diseases or cognitive disorders which could interfere with treatment and follow-up

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead
• The First Affiliated Hospital of Guangzhou Medical University: collaborator
• Ruijin Hospital: collaborator

Study Sites (3)

The First Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, China

Location

Ruijin Hospital, Shanghai Jiao Tong University

Shanghai, Shanghai Municipality, China

Location

Shanghai Zhongshan Hospital

Shanghai, Shanghai Municipality, China

Location

Related Publications (1)

• Hua JL, Yang ZF, Cheng QJ, Han YP, Li ZT, Dai RR, He BF, Wu YX, Zhang J. Prevention of exacerbation in patients with moderate-to-very severe COPD with the intent to modulate respiratory microbiome: a pilot prospective, multi-center, randomized controlled trial. Front Med (Lausanne). 2024 Jan 5;10:1265544. doi: 10.3389/fmed.2023.1265544. eCollection 2023.

  PMID: 38249987 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Probiotics

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Jing Zhang, MD, PhD

  Shanghai Zhongshan Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Although this study is unblinded, we will adopt method of allocation concealment to reduce selection bias.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants are equally assigned to four groups in parallel to accept oral probiotics, aerosol inhaled amikacin, combined vaccination or blank control for the duration of the study.

Study Record Dates

• First Submitted: February 12, 2018
• First Posted: February 28, 2018
• Study Start: December 1, 2018
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2020
• Last Updated: June 23, 2022

Record last verified: 2018-11

Locations

CN (3)