UMIN-CTR Clinical Trial

Public title

Lung volume reduction procedures for severe emphysematous COPD: Bayesian network meta-analysis

Acronym

Lung volume reduction procedures for severe emphysematous COPD: Bayesian network meta-analysis

Scientific Title

Lung volume reduction procedures for severe emphysematous COPD: Bayesian network meta-analysis

Scientific Title:Acronym

Lung volume reduction procedures for severe emphysematous COPD: Bayesian network meta-analysis

Region

Japan

North America

Condition

severe emphysematous COPD

Classification by specialty

Pneumology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

Mechanical lung volume reduction has been considered as one of the treatment strategies for COPD with advanced emphysema. Lung volume reduction surgery (LVRS) was established in early 2000s. Since then, various bronchoscopic procedures, such as endobronchial valve (EBV), intrabronchial valve (IBV), endobronchial coils (EBC), bronchoscopic thermal vapour ablation (TVA), stent airway bypass (SAB ), and emphysematous lung sealant (ELS), have been developed. However, in most studies, patients were randomly allocated into either the novel intervention or medical treatment arms; making direct comparisons of these newly developed treatments rare. Network meta-analysis is the preferred research approach for ranking several volume reduction procedures and providing clinically useful data. To our knowledge, two frequentist network meta-analysis (NMA) evaluating bronchoscopic lung volume reduction procedures, each including 10 or 13 trials, presented partially inconsistent results with each other in 2020. Subsequently, the number of randomised controlled trials (RCTs) on this topic more than doubled by 2023. The current systematic review and Bayesian NMA was designed to compare and rank the efficacy and safety of lung volume reduction procedures, including LVRS, for severe emphysematous COPD.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Primary and secondary outcomes will be assessed for a "middle-term" follow-up period. The preferred follow-up time is 6 months after the intervention; however, in case where data for 6 months are missing, a substitute using the data with the longest observation between 3 and 6 months will be allowed.
The co-primary outcomes include middle-term pulmonary function (mean difference [MD] in FEV1 change from baseline, in mL), quality of life (MD in St. George Respiratory Questionnaire [SGRQ] change from baseline, in points), physical activity (MD in 6-minute walking distance [6MWD] change from baseline, in meters), and mortality (risk ratio [RR] for all-cause death). A COPD specific SGRQ will not be utilized in our study.

Key secondary outcomes

With the exception of long-term survival (5-year mortality), all secondary outcomes will be assessed for a "middle-term" follow-up period. The preferred follow-up time is 6 months after the intervention; however, in case where data for 6 months are missing, a substitute using the data with the longest observation between 3 and 6 months will be allowed.
Secondary outcomes include long-term mortality (RR for all-cause death over 5 years), middle-term severe/serious adverse events (SAE, RR), pneumothorax (RR), and exacerbation (RR). Variations in the definition of exacerbation such as, "acute exacerbation" will be accepted.

Study type

Others,meta-analysis etc

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

Purpose of intervention

Type of intervention

Interventions/Control_1

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

Not applicable

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

The primary focus of this systematic review is on patients with severe emphysematous COPD. The term "emphysema" refers to pathological changes of the lung, while the clinical diagnosis is referred to as COPD. However, inclusion criteria strictly based on the COPD diagnosis appeared to exclude historically pivotal RCTs that enrolled patients regardless of their COPD diagnosis. Given the substantial overlap between emphysema and COPD, our study does not require patients to have an explicit COPD diagnosis as long as their clinical characteristics align with COPD.

Key exclusion criteria

For instance, studies with a mean or median forced expiratory volume in 1 second (FEV1)/forced vital capacity exceeding 70% will be excluded.

Target sample size

Name of lead principal investigator

1st name	Nobuyuki
Middle name
Last name	Horita

Organization

Yokohama City University

Division name

Chemotherapy Center

Zip code

235-0004

Address

3-9, Fukuura, Kanazawa, Yokohama, Japan

TEL

045-787-2800

Email

horitano@yokohama-cu.ac.jp

Name of contact person

1st name	Nobuyuki
Middle name
Last name	Horita

Organization

Yokohama City University Hospital

Division name

Chemotherapy Center

Zip code

235-0004

Address

3-9, Fukuura, Kanazawa, Yokohama, Japan

TEL

045-787-2800

Homepage URL

Email

horitano@yokohama-cu.ac.jp

Institute

Yokohama City University

Institute

Department

Personal name

Organization

Yokohama City University

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

IRB approval is not required.

Address

IRB approval is not required.

Tel

045-787-2800

Email

horitano@yokohama-cu.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2023

Year

09

Month

09

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Preinitiation

Date of protocol fixation

2023

Year

09

Month

09

Day

Date of IRB

Anticipated trial start date

2023

Year

09

Month

09

Day

Last follow-up date

2024

Year

12

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

[Subgroup analysis] For the four primary outcomes, we plan to conduct subgroup analysis using studies for heterogeneous emphysema without collateral ventilation.
[Quality assessment] Bias within studies will be assessed using the Revised Tool for Assessing Risk of Bias in Randomised Trials (RoB2). Then, Confidence in Network Meta-Analysis (CINeMA) will be applied to evaluate the overall reliability of the evidence derived from the network.
[Data Synthesis and Statistical Analysis] A Bayesian NMA, grounded in a random effects model, serves as the backbone of our meta-analysis. We will apply weakly-informative prior distributions for various comparisons and outcome types. Continuous variables will undergo analysis using mean difference (MD) and a 95% credible interval (CrI). Conversely, binary variables related to event, such as the incidence of deaths and adverse events (AEs), will undergo analysis using the risk ratio (RR) and a 95% CrI. All analyses engage JAGS (Just Another Gibbs Sampler, Ver. 4.3.1) for executing Markov Chain Monte Carlo (MCMC) simulations, leveraging the R packages 'Rjags' and 'Gemtc'.

Registered date

2023

Year

09

Month

09

Day

Last modified on

2023

Year

09

Month

09

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000059530