Study 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.
High-Intensity vs Low-Intensity NPPV in Patients With an AECOPD: The HAPPEN Trial
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
1 other identifier
interventional
300
1 country
31
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
Started Jan 2019
Longer than P75 for not_applicable
31 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 2, 2016
CompletedFirst Posted
Study publicly available on registry
December 7, 2016
CompletedStudy Start
First participant enrolled
January 3, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 31, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
April 22, 2022
CompletedFebruary 7, 2024
February 1, 2024
3.1 years
December 2, 2016
February 4, 2024
Conditions
Outcome Measures
Primary Outcomes (1)
The need for endotracheal intubation during hospitalization
Defined as the proportion of patients who needed for endotracheal intubation during hospitalization after randomization
From randomization to discharge from hospital
Secondary Outcomes (15)
Actual intubation during hospitalization
From randomization to discharge from hospital
Need for endotracheal intubation at day 28
Within 28 days since randomization
Actual intubation at day 28
Within 28 days since randomization
The composite of actual intubation or avoiding intubation by crossover to high-intensity NPPV
From randomization to discharge from hospital
NPPV weaning success
From randomization to discharge from hospital
- +10 more secondary outcomes
Study Arms (2)
High-intensity NPPV
EXPERIMENTALPatients will receive high-intensity NPPV.
Low-intensity NPPV
ACTIVE COMPARATORPatients will receive low-intensity NPPV.
Interventions
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.
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.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (31)
Wuyuan Hospital of Inner Mongolia
Bayan Nur, China
Beijing Chao-Yang Hospital
Beijing, China
Beijing Fangshan Liangxiang Hospital,
Beijing, China
Beijing Jingmei Group General Hospital
Beijing, China
Beijing Luhe Hospital
Beijing, China
Beijing Mentougou District Hospital
Beijing, China
Beijing Pinggu Hospital
Beijing, China
Beijing Zhongguancun Hospital
Beijing, China
Capital Medical University Daxing Teaching Hospital
Beijing, China
The Second Affiliated Hospital of Chongqing Medical University
Chongqing, China
Dalian Friendship Hospital
Dalian, China
Dalian Municipal Central Hospital
Dalian, China
Shulan (Hang Zhou) Hospital
Hangzhou, China
Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
Hangzhou, China
Hemei General Hospital
Hebi, China
Huangshi Central Hospital
Huangshi, China
Jiaozuo People's Hospital
Jiaozuo, China
Jiaozuo Second Hospital
Jiaozuo, China
Kaifeng Central Hospital
Kaifeng, China
The First Affiliated Hospital of Hanan University,
Kaifeng, China
The First People's Hospital of Luoyang
Luoyang, China
The Third Hospital of Mianyang
Mianyang, China
Nanyang Central Hospital
Nanyang, China
Nanyang First People's Hospital
Nanyang, China
Sanmenxia Central Hospital
Sanmenxia, China
The Second Hospital of Tongliao
Tongliao, China
People's Hospital of Xinjiang Uygur Autonomous Region
Ürümqi, China
Xinxiang Central Hospital
Xinxiang, China
Zhengzhou Central Hospital
Zhengzhou, China
Hunan Province Directly Affiliated TCM Hospital
Zhuzhou, China
Zibo First Hospital
Zibo, China
Related Publications (2)
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.
PMID: 39283649DERIVEDLuo 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.
PMID: 30463622DERIVED
Study Officials
- PRINCIPAL INVESTIGATOR
Zujin Luo, MD
Beijing Chao Yang Hospital
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
December 2, 2016
First Posted
December 7, 2016
Study Start
January 3, 2019
Primary Completion
January 31, 2022
Study Completion
April 22, 2022
Last Updated
February 7, 2024
Record last verified: 2024-02
Data Sharing
- IPD Sharing
- Will not share