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

NCT ID: NCT03449459

Last Updated: 2022-06-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 144 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-01
• Study Completion Date: 2020-12-01

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.

Detailed Description

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease characterized by incomplete reversible airflow limitation, small airway obstruction and alveolar structural damage. About 3 million patients die from COPD every year around the world. The prevalence of COPD in Chinese people over the age of 40 is as high as 12 % and has risen by 50 % in the past nine years.

Acute exacerbation is the leading cause of death in patients with COPD , and accounts for a majority of expenditure of COPD management. The colonization of potential pathogenic bacteria in the lower respiratory tract is an important cause of the acute exacerbation especially in patients with moderate and severe COPD.

Some clinical studies show that aerosol inhaled antibiotics is promising in reducing acute exacerbation, but these exploratory studies have some defects so that they can't back up for the clinical application of aerosol inhaled antibiotics. Amikacin, a kind of aminoglycosides, is sensitive to the common pathogens of acute exacerbation of COPD in China. Therefore it is necessary to carry out a clinical trial to verify its efficacy and safety in pathogen decolonization and prevention of acute exacerbation.

In addition, owing to bacterial resistance and insufficient antibiotics concentration in lower respiratory tract, developing new antibacterial materials is necessary. Oral probiotics is an another way to regulate the bacterial load and inflammatory response in lower respiratory tract, which has been proven to effectively prevent acute exacerbation in cystic fibrosis and childhood asthma. Likewise, airway bacterial burden and inflammation are two main mechanisms of acute exacerbation in COPD. Hence, considering its convenience and safety of oral probiotics, we perform a trial to make clinical evaluation for it.

What's more, influenza and streptococcus pneumoniae vaccines are separately recommended for patients with COPD in the Global Initiative for Chronic Obstructive Pulmonary Disease(GOLD), but there have been no studies on the effects of combined vaccination on bacterial decolonization in lower respiratory tract or on the prevention of acute exacerbation.

Effects of these above methods on the decolonization of potential pathogenic bacteria in lower respiratory tract and the inflammatory reaction are not clear. 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)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

oral probiotics

Group Type: EXPERIMENTAL

oral probiotics

Intervention Type: 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.

aerosol inhaled amikacin

Group Type: EXPERIMENTAL

aerosol inhaled amikacin

Intervention Type: 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.

combined vaccination

Group Type: EXPERIMENTAL

combined vaccination

Intervention Type: 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.

conventional therapy (blank control)

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

oral probiotics

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.

Intervention Type: DIETARY_SUPPLEMENT

aerosol inhaled amikacin

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.

Intervention Type: DRUG

combined vaccination

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.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Written informed consent must be obtained before any assessment is performed

2. Male or female adults aged 18-65 years

3. 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)

4. Moderate to very severe airflow limitation (post-bronchodilator FEV1 < 80% of the predicted normal value)

5. 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.

6. In the stable stage of COPD

Exclusion Criteria

1. 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

2. Patients who are in critical conditions

3. 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

4. Patients with concomitant pulmonary disease (including but not limited to bronchiectasis, interstitial lung disease, asthma)

5. Patients who are highly likely to be lost during the 3-month treatment and the 1-year follow up

6. Pregnant or nursing (lactating) women

7. Patients who have been vaccinated against influenza in the current year, or against Streptococcus pneumoniae within five years, or have vaccination contraindications

8. Patients who are allergic to amikacin or other aminoglycosides

9. Patients who have participated in any interventional clinical trials in the three months prior to screening

10. Patients with mental diseases or cognitive disorders which could interfere with treatment and follow-up

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The First Affiliated Hospital of Guangzhou Medical University

OTHER

Sponsor Role: collaborator

Ruijin Hospital

OTHER

Sponsor Role: collaborator

Shanghai Zhongshan Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jing Zhang, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Shanghai Zhongshan Hospital

Locations

The First Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, China

Ruijin Hospital, Shanghai Jiao Tong University

Shanghai, Shanghai Municipality, China

Shanghai Zhongshan Hospital

Shanghai, Shanghai Municipality, China

Countries

China

References

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.

Reference Type: DERIVED

PMID: 38249987 (View on PubMed)

Other Identifiers

2017YFC1309303

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

B2017-197R

Identifier Type: -

Identifier Source: org_study_id