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

Acute Exacerbation of Chronic Obstructive Pulmonary Disease Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02985918
• Other study ID #: BeijingCYH-ICU-004
• Status: Terminated
• Phase: N/A
• Start date: January 3, 2019
• Est. completion date: April 22, 2022

Study information

• Verified date: February 2024
• Source: Beijing Chao Yang Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 300
• Est. completion date: April 22, 2022
• Est. primary completion date: January 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Exacerbation of Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

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.
• 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.

Locations

Country	Name	City	State
China	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	Urumqi
China	Xinxiang Central Hospital	Xinxiang
China	Zhengzhou Central Hospital	Zhengzhou
China	Hunan Province Directly Affiliated TCM Hospital	Zhuzhou
China	Zibo First Hospital	Zibo

Sponsors (1)

Lead Sponsor	Collaborator
Beijing Chao Yang Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Actual intubation during hospitalization	Defined as the proportion of patients actually receiving intubation and invasive ventilation during hospitalization after randomization	From randomization to discharge from hospital
Secondary	Need for endotracheal intubation at day 28	Defined as the proportion of patients who needed endotracheal intubation within 28 days since randomization	Within 28 days since randomization
Secondary	Actual intubation at day 28	Defined as the proportion of patients receiving intubation and invasive ventilation within 28 days after randomization	Within 28 days since randomization
Secondary	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	From randomization to discharge from hospital
Secondary	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	From randomization to discharge from hospital
Secondary	Mortality in hospital		From randomization to discharge from hospital
Secondary	Mortality at day 28		Within 28 days since randomization
Secondary	Mortality at day 90		Within 90 days since randomization
Secondary	Intensive care unit admission	Defined as the proportion of patients who transferred to ICU during hospitalization after randomization	From randomization to discharge from hospital
Secondary	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.	From randomization to discharge from hospital
Secondary	Length of hospital stay	Defined as the number of days for the index hospitalization	From hospital admission to discharge
Secondary	Length of hospital stay after randomization	Defined as the number of hospitalization days since randomization	From randomization to discharge from hospital
Secondary	Invasive ventilator-free days at day 28	Defined as 28 minus the number of days with invasive ventilator (range, 0-28 days) since randomization	Within 28 days since randomization
Secondary	ICU-free days at day 28	Defined as 28 minus the number of days in the ICU (range, 0-28 days) since randomization	Within 28 days since randomization
Secondary	Hospital readmission at day 90	Defined as the number of hospitalization days within 90 days since randomization	Within 90 days since randomization