High-Intensity vs Low-Intensity NPPV in Patients With an AECOPD: The HAPPEN Trial

February 4, 2024 updated by: Zujin Luo, Beijing Chao Yang Hospital

Effect of High-Intensity vs Low-Intensity Noninvasive Positive Pressure Ventilation on the Need for Endotracheal Intubation in Patients With an Acute Exacerbation of Chronic Obstructive Pulmonary Disease The HAPPEN Randomized Clinical Trial

To determine whether high-intensity NPPV, compared with low-intensity NPPV, could reduce the need for endotracheal intubation during hospitalization in patients with an AECOPD and hypercapnia.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
300

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Bayan Nur, China
        • Wuyuan Hospital of Inner Mongolia
      • Beijing, China
        • Beijing Luhe Hospital
      • Beijing, China
        • Beijing Chao-Yang Hospital
      • Beijing, China
        • Beijing Pinggu Hospital
      • Beijing, China
        • Beijing Mentougou District Hospital
      • Beijing, China
        • Beijing Fangshan Liangxiang Hospital,
      • Beijing, China
        • Beijing Jingmei Group General Hospital
      • Beijing, China
        • Beijing Zhongguancun Hospital
      • Beijing, China
        • Capital Medical University Daxing Teaching Hospital
      • Chongqing, China
        • The Second Affiliated Hospital of Chongqing Medical University
      • Dalian, China
        • Dalian Friendship Hospital
      • Dalian, China
        • Dalian Municipal Central Hospital
      • Hangzhou, China
        • Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
      • Hangzhou, China
        • Shulan (Hang Zhou) Hospital
      • Hebi, China
        • Hemei General Hospital
      • Huangshi, China
        • Huangshi Central Hospital
      • Jiaozuo, China
        • Jiaozuo People's Hospital
      • Jiaozuo, China
        • Jiaozuo Second Hospital
      • Kaifeng, China
        • Kaifeng Central Hospital
      • Kaifeng, China
        • The First Affiliated Hospital of Hanan University,
      • Luoyang, China
        • The First People's Hospital of Luoyang
      • Mianyang, China
        • The Third Hospital of Mianyang
      • Nanyang, China
        • Nanyang Central Hospital
      • Nanyang, China
        • Nanyang First People's Hospital
      • Sanmenxia, China
        • Sanmenxia Central Hospital
      • Tongliao, China
        • The Second Hospital of Tongliao
      • Urumqi, China
        • People's Hospital of Xinjiang Uygur Autonomous Region
      • Xinxiang, China
        • Xinxiang Central Hospital
      • Zhengzhou, China
        • Zhengzhou Central Hospital
      • Zhuzhou, China
        • Hunan Province Directly Affiliated TCM Hospital
      • Zibo, China
        • Zibo First Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • AECOPD confirmed by the 2019 criteria of the Global Initiative for Chronic Obstructive Lung Disease (GOLD)
  • Arterial pH <7.35 and PaCO2 >45 mmHg at screening entry
  • PaCO2 >45 mmHg after a 6-hour trial of low-intensity NPPV

Exclusion Criteria:

  • Age <18 years
  • Excessive respiratory secretions with weak cough
  • Upper airway obstruction
  • Recent oral, facial, or cranial trauma or surgery
  • Recent gastric or esophageal surgery
  • Presence of restrictive ventilatory dysfunction (eg, consolidation or removal of at least one pulmonary lobe, massive pleural effusion, chest wall deformity, continuous strapping with thoracic or abdominal bandage, or severe abdominal distension)
  • Active upper gastrointestinal bleeding
  • Cardiac or respiratory arrest
  • Arterial oxygen tension/fraction of inspired oxygen (PaO2/FiO2) <100 mmHg
  • Pneumothorax
  • Obvious emphysematous bullae confirmed by chest CT scan
  • Ventricular arrhythmia or myocardial ischemia
  • Severe hemodynamic instability (mean arterial pressure <65 mmHg)
  • Severe metabolic acidosis (pH <7.20 and bicarbonate <22 mmol/L)
  • Refusal to receive NPPV or give informed consent
  • Prior endotracheal intubation or tracheostomy during the current hospitalization
  • A do-not-intubate order

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: High-intensity NPPV
Patients will receive high-intensity NPPV.
Device: High-intensity NPPV
In the high-intensity NPPV group, IPAP is initially adjusted in increments/decrements of 1-2 cmH2O, typically ranging from 20 to 30 cmH2O (or a tolerated maximum), to obtain a VT 10-15 mL/kg PBW and a respiratory rate <25 breaths/min. Subsequent adjustments to IPAP are based on the results of arterial blood gases (ABGs; up to 30 cmH2O) to achieve normocapnia (if possible), or to maximally decrease PaCO2 toward normocapnia if normocapnia can not be achieved. If PaCO2 decreases to less than 35 mmHg, IPAP will be decreased to achieve normocapnia.
Active Comparator: Low-intensity NPPV
Patients will receive low-intensity NPPV.
Device: Low-intensity NPPV
In the low-intensity NPPV group, as well as during the 6-hour trial of low-intensity NPPV, IPAP is initially adjusted in increments/decrements of 1-2 cmH2O (up to 20 cmH2O), according to patients' tolerance, to obtain a VT 6-10 mL/kg PBW and a respiratory rate <25 breaths/min. Subsequent adjustments to IPAP are based on the results of ABGs (up to 20 cmH2O) to achieve a pH of ≥7.35 and to reduce PaCO2 to a level deemed appropriate by the attending physician.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
The need for endotracheal intubation during hospitalization
Time Frame: From randomization to discharge from hospital
Defined as the proportion of patients who needed for endotracheal intubation during hospitalization after randomization
From randomization to discharge from hospital

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Actual intubation during hospitalization
Time Frame: From randomization to discharge from hospital
Defined as the proportion of patients actually receiving intubation and invasive ventilation during hospitalization after randomization
From randomization to discharge from hospital
Need for endotracheal intubation at day 28
Time Frame: Within 28 days since randomization
Defined as the proportion of patients who needed endotracheal intubation within 28 days since randomization
Within 28 days since randomization
Actual intubation at day 28
Time Frame: Within 28 days since randomization
Defined as the proportion of patients receiving intubation and invasive ventilation within 28 days after randomization
Within 28 days since randomization
The composite of actual intubation or avoiding intubation by crossover to high-intensity NPPV
Time Frame: From randomization to discharge from hospital
Defined as the incidence of patients receiving actual intubation in the high-intensity NPPV group vs the composite incidence of actual intubation or avoiding intubation by crossover to high-intensity NPPV in case of intubation criteria in the low-intensity NPPV group) during hospitalization after randomization
From randomization to discharge from hospital
NPPV weaning success
Time Frame: From randomization to discharge from hospital
Defined as the proportion of patients with persistent disconnection of NPPV without the presence of respiratory distress within the following 72 hours during hospitalization after randomization
From randomization to discharge from hospital
Mortality in hospital
Time Frame: From randomization to discharge from hospital
From randomization to discharge from hospital
Mortality at day 28
Time Frame: Within 28 days since randomization
Within 28 days since randomization
Mortality at day 90
Time Frame: Within 90 days since randomization
Within 90 days since randomization
Intensive care unit admission
Time Frame: From randomization to discharge from hospital
Defined as the proportion of patients who transferred to ICU during hospitalization after randomization
From randomization to discharge from hospital
Live discharge from the hospital
Time Frame: From randomization to discharge from hospital
Defined as the proportion of patients with the exception of those who died and withdrawn treatment therapy during hospitalization after randomization.
From randomization to discharge from hospital
Length of hospital stay
Time Frame: From hospital admission to discharge
Defined as the number of days for the index hospitalization
From hospital admission to discharge
Length of hospital stay after randomization
Time Frame: From randomization to discharge from hospital
Defined as the number of hospitalization days since randomization
From randomization to discharge from hospital
Invasive ventilator-free days at day 28
Time Frame: Within 28 days since randomization
Defined as 28 minus the number of days with invasive ventilator (range, 0-28 days) since randomization
Within 28 days since randomization
ICU-free days at day 28
Time Frame: Within 28 days since randomization
Defined as 28 minus the number of days in the ICU (range, 0-28 days) since randomization
Within 28 days since randomization
Hospital readmission at day 90
Time Frame: Within 90 days since randomization
Defined as the number of hospitalization days within 90 days since randomization
Within 90 days since randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Beijing Chao Yang Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Zujin Luo, MD, Beijing Chao Yang Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 3, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 31, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 22, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 2, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 5, 2016

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 7, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 7, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 4, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • BeijingCYH-ICU-004

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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