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Acute Exacerbation of Chronic Obstructive Pulmonary DiseaseNCT02985918

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

A study testing High-intensity NPPV and Low-intensity NPPV in people with Acute Exacerbation of Chronic Obstructive Pulmonary Disease, run by Beijing Chao Yang Hospital at 31 sites in China.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
High-intensity NPPV and Low-intensity NPPV
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
300 participants
Where
31 sitesChina
Study dates
3 Jan 2019to 22 Apr 2022
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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)
Show all 17Show fewer
  • 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

Trial locations and contacts

31 sites in 1 country.

31 sites in 1 country

China31 sites

  • Wuyuan Hospital of Inner Mongolia

    Bayan Nur

  • Beijing Chao-Yang Hospital

    Beijing

  • Beijing Fangshan Liangxiang Hospital,

    Beijing

  • Beijing Jingmei Group General Hospital

    Beijing

  • Beijing Luhe Hospital

    Beijing

  • Beijing Mentougou District Hospital

    Beijing

  • Beijing Pinggu Hospital

    Beijing

  • Beijing Zhongguancun Hospital

    Beijing

  • Capital Medical University Daxing Teaching Hospital

    Beijing

  • The Second Affiliated Hospital of Chongqing Medical University

    Chongqing

  • Dalian Friendship Hospital

    Dalian

  • Dalian Municipal Central Hospital

    Dalian

  • Shulan (Hang Zhou) Hospital

    Hangzhou

  • Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

    Hangzhou

  • Hemei General Hospital

    Hebi

  • Huangshi Central Hospital

    Huangshi

  • Jiaozuo People's Hospital

    Jiaozuo

  • Jiaozuo Second Hospital

    Jiaozuo

  • Kaifeng Central Hospital

    Kaifeng

  • The First Affiliated Hospital of Hanan University,

    Kaifeng

  • The First People's Hospital of Luoyang

    Luoyang

  • The Third Hospital of Mianyang

    Mianyang

  • Nanyang Central Hospital

    Nanyang

  • Nanyang First People's Hospital

    Nanyang

  • Sanmenxia Central Hospital

    Sanmenxia

  • The Second Hospital of Tongliao

    Tongliao

  • People's Hospital of Xinjiang Uygur Autonomous Region

    Ürümqi

  • Xinxiang Central Hospital

    Xinxiang

  • Zhengzhou Central Hospital

    Zhengzhou

  • Hunan Province Directly Affiliated TCM Hospital

    Zhuzhou

  • Zibo First Hospital

    Zibo

Other trials in China

About this study

Official title: 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.

Being tested
High-intensity NPPV, Low-intensity NPPV

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • High-intensity NPPVDevice

    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.

  • Low-intensity NPPVDevice

    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.

Study groups in NCT02985918
Study groupRoleWhat they receive
High-intensity NPPVExperimentalPatients will receive high-intensity NPPV.
Receives: Device: High-intensity NPPV
Low-intensity NPPVActive comparatorPatients will receive low-intensity NPPV.
Receives: Device: Low-intensity NPPV

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The need for endotracheal intubation during hospitalization

    Defined as the proportion of patients who needed for endotracheal intubation during hospitalization after randomization

    Measured: From randomization to discharge from hospital

Secondary outcomes (15)

  1. Actual intubation during hospitalization

    Defined as the proportion of patients actually receiving intubation and invasive ventilation during hospitalization after randomization

    Measured: From randomization to discharge from hospital

  2. Need for endotracheal intubation at day 28

    Defined as the proportion of patients who needed endotracheal intubation within 28 days since randomization

    Measured: Within 28 days since randomization

  3. Actual intubation at day 28

    Defined as the proportion of patients receiving intubation and invasive ventilation within 28 days after randomization

    Measured: Within 28 days since randomization

  4. The composite of actual intubation or avoiding intubation by crossover to high-intensity NPPV

    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

    Measured: From randomization to discharge from hospital

  5. NPPV weaning success

    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

    Measured: From randomization to discharge from hospital

  6. Mortality in hospital

    Measured: From randomization to discharge from hospital

  7. Mortality at day 28

    Measured: Within 28 days since randomization

  8. Mortality at day 90

    Measured: Within 90 days since randomization

  9. Intensive care unit admission

    Defined as the proportion of patients who transferred to ICU during hospitalization after randomization

    Measured: From randomization to discharge from hospital

  10. Live discharge from the hospital

    Defined as the proportion of patients with the exception of those who died and withdrawn treatment therapy during hospitalization after randomization.

    Measured: From randomization to discharge from hospital

  11. Length of hospital stay

    Defined as the number of days for the index hospitalization

    Measured: From hospital admission to discharge

  12. Length of hospital stay after randomization

    Defined as the number of hospitalization days since randomization

    Measured: From randomization to discharge from hospital

  13. Invasive ventilator-free days at day 28

    Defined as 28 minus the number of days with invasive ventilator (range, 0-28 days) since randomization

    Measured: Within 28 days since randomization

  14. ICU-free days at day 28

    Defined as 28 minus the number of days in the ICU (range, 0-28 days) since randomization

    Measured: Within 28 days since randomization

  15. Hospital readmission at day 90

    Defined as the number of hospitalization days within 90 days since randomization

    Measured: Within 90 days since randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Dec 2016 (estimated)
  2. Study start3 Jan 2019
  3. Primary completion31 Jan 2022
  4. Study completion22 Apr 2022

Why it stopped: The trial has been terminated by the DSMB and the trial steering committee, based on the interim analysis results and the impracticality of continuing the trial in the context of the coronavirus disease 2019 (COVID-19) pandemic.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Outcomes assessor
Enrolment
300 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02985918
Sponsor's protocol ID
BeijingCYH-ICU-004
Status last verified
Feb 2024
First submitted
2 Dec 2016
Last updated
7 Feb 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Luo Z, Li Y, Li W, Li Y, Nie Q, Shi Y, Wang J, Ji Q, Han X, Liu S, Li D, Wang S, Li Z, Jia D, Ge H, Xu P, Feng Z, Li F, An F, Tai N, Yue L, Xie H, Jin X, Liu H, Dang Q, Zhang Y, Sun L, Wang J, Huang H, Chen L, Ma Y, Cao Z, Wang C; HAPPEN Investigators. 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. JAMA. 2024 Nov 26;332(20):1709-1722. doi: 10.1001/jama.2024.15815.

    PubMed 39283649

  • Luo Z, Wu C, Li Q, Zhu J, Pang B, Shi Y, Ma Y, Cao Z; HAPPEN collaboration group. High-intensity versus low-intensity noninvasive positive pressure ventilation in patients with acute exacerbation of chronic obstructive pulmonary disease (HAPPEN): study protocol for a multicenter randomized controlled trial. Trials. 2018 Nov 21;19(1):645. doi: 10.1186/s13063-018-2991-y.

    PubMed 30463622

Questions about this trial

What is this clinical trial studying?

A study testing High-intensity NPPV and Low-intensity NPPV in people with Acute Exacerbation of Chronic Obstructive Pulmonary Disease, run by Beijing Chao Yang Hospital at 31 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 7 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 31 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study was stopped early (reason given: The trial has been terminated by the DSMB and the trial steering committee, based on the interim analysis results and the impracticality of continuing the trial in the context of the coronavirus disease 2019 (COVID-19) pandemic.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The need for endotracheal intubation during hospitalization (time frame: From randomization to discharge from hospital). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02985918, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Feb 2024.

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