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Japanese, multicenter, randomized controlled trial of noninvasive positive pressure ventilation (NPPV) versus high-flow nasal cannula oxygen therapy (HFNC) for severe acute hypoxemic respiratory failure (Ja-NP-Hi trial)

Ja-NP-Hi trial (Ja-NP-Hi trial)

85

NPPV group (38 patients) Number of subjects (%): male 27 (71.1), female 11 (28.9) Age, median (IQR), yr: 77.00 (71.00, 82.00) BMI median (IQR): 22.23 (19.48, 24.38) Smoking history, number (%): current smoker 6 (15.8), ex-smoker 19 (50.0), never smoker 13 (34.2) PaO2/FiO2, median (IQR): 166.44 (131.20, 205.69) SOFA score, median (IQR): 4.00 (3.00, 4.00) HFNC group (47 patients) Number of subjects (%): male 34 (72.3), female 13 (27.7) Age, median (IQR), yr: 71.00 (65.00, 79.50) BMI median (IQR): 23.15 (20.60, 25.43) Smoking history, number (%): current smoker 9 (19.1), ex-smoker 24 (51.1), never smoker 14 (29.8) PaO2/FiO2, median (IQR): 182.60 (152.00, 220.62) SOFA score, median (IQR): 3.00 (3.00, 4.00)

Eighty-five patients were enrolled between October 2017 and March 1, 2021. The pace of enrollment was slower than originally projected and was further slowed by the COVID-19 disaster, so the target number of patients was not reached. 38 patients were assigned to the NPPV group and 47 to the HFNC group.

The number of serious adverse events (SAEs) was 2 in the NPPV group and 2 in the HFNC group. There were no cases of SAEs that could not be ruled out as being causally related to the study treatment, NPPV or HFNC (falling under the category of diseases suspected to be caused by the implementation of clinical research based on the relevant research protocol as per Article 13 of the Clinical Research Law).

(Primary endpoint) Patients in the NPPV group had a significantly longer time to meet the intubation criteria in the first 28 days of treatment compared to patients in the HFNC group (hazard ratio 0.327 (P=0.006), 95% confidence interval 0.148-0.724). (Secondary endpoints) There was no significant difference in the time to intubation in the first 28 days of treatment between the two groups (P value = 0.470). There was no significant difference in the time to intubation in the first 28 days of treatment between the two groups (P=0.470), even after adjustment for age and PaO2/FiO2 at enrollment (P=0.256). There was no significant difference in the time to death at 28 days between the two groups (P=0.363). There was no significant difference in time to death at 28 days between the two groups (P=0.363), even after adjustment for age and PaO2/FiO2 at enrollment (P=0.624). There was no significant difference in the time to in-hospital death between the two groups (P=0.378). There was no significant difference in time to in-hospital death between the two groups (P=0.378), even after adjustment for age and PaO2/FiO2 at enrollment (P=0.366). There was no significant difference in ventilator-free days (ventilator: intubation ventilation) between the two groups (P=0.744). There was no significant difference in ventilator-free days (ventilator: intubation ventilation) between the two groups (P=0.744). Pulmonary oxygenation performance (PaO2/FIO2 ratio) was significantly better in the NPPV group than in the HFNC group at 30 minutes, 4 hours, and 24 hours after the start of treatment (P<0.001, <0.001, 0.028). There was no significant difference in blood pressure, respiratory rate, or pulse rate between the two groups. There was no significant difference in blood pressure, respiratory rate, or pulse rate between the two groups. pH in arterial blood gas analysis was significantly lower in the NPPV group than in the HFNC group at 4 hours and 24 hours after the start of treatment (P=0.009, 0.025). PaCO2 in arterial blood gas analysis was significantly higher in the NPPV group than in the HFNC group at 4 hours and 24 hours after the start of treatment (P=0.005, 0.031). There was no significant difference in the duration of any respiratory management (NPPV, HFNC, intubation) between the two groups (P=0.391) (adjusted for age and PaO2/FiO2 at enrollment). There was no significant difference in the duration of total respiratory hospitalization between the two groups (P=0.792) (adjusted for age and PaO2/FiO2 at enrollment). There were 3 adverse events in the NPPV group and 2 in the HFNC group that could not be ruled out as being causally related to protocol treatment. Continuous sedation was used in 14 patients (36.84%) in the NPPV group and 3 patients (6.38%) in the HFNC group.

For patients with acute hypoxemic respiratory failure, the time to meet the intubation criteria was significantly longer in the NPPV group than in the HFNC group. During multiple observation periods, pulmonary oxygenation capacity (PaO2/FiO2) was significantly better, pH was significantly lower and PaCO2 was significantly higher in the NPPV group. There were few adverse events that could not be ruled out as being causally related to protocol treatment in both groups.

June. 01, 2022

No

No

https://jrct.mhlw.go.jp/latest-detail/jRCTs052180236

Tomii Keisuke

Kobe City Medical Center General Hospital

2-1-1, Minatojima-minamimachi, Chuo-ku, Kobe City, Hyogo Prefecture

ktomii@kcho.jp

Nagata Kazuma

Kobe City Medical Center General Hospital

2-1-1, Minatojima-minamimachi, Chuo-ku, Kobe City, Hyogo Prefecture

+81-78-302-4321

kazuma_n1101@yahoo.co.jp

Complete

Oct. 01, 2017

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

1. Patients who have acute respiratory failure, which occures within 1 week of a known clinical insult or new or worsening respiratory symptoms.
2. Patients who have new infiltrates on chest radiography.
3. Patients with PaO2/FIO2 < 300 at screening.
4. Patients with PaCO2 <= 45 Torr at screening.
5. Patients who are more than 20 years old at the time of the informed consent.
6. Patients who agree to participate in the study with the written informed consent.

1. Patients with urgent need for endotracheal intubation.
2. Patients with respiratory failure fully explained by cardiac failure or fluid overload.
3. Patients with COVID-19.
4. Patients with exacerbation of asthma.
5. Patients with pulmonary embolism.
6. Patients who have received NPPV or HFNC for more than 24 hours at the time of the informed consent.
7. Patients who have the following chronic pulmonary disease.
a. Chronic interstitial pneumonia apparent on chest radiography.
b. Chronic pulmonary disease affecting the efficacy endpoints (for example; COPD, tuberculosis sequelae, bronchiectasis, pneumoconiosis etc.).
c. Chronic respiratory failure with need for home oxygen therapy (more than 12 hours/day).
d. Chronic pulmonary disease that are regarded as inadequate for the study by the investigators.
8. Patients with active malignant tumor affecting the efficacy endpoints.
9. Patients with contraindications either to NPPV or HFNC, such as undrained pneumothorax, upper airway obstruction, facial trauma, injury and deformity etc.
10. Patients with major surgery within 4 weeks prior to the time of the informed consent.
11. Patients with severe leukopenia (WBC < 1000 per microliter of blood).
12. Patients with hemodynamic instability (systolic blood pressure < 90 mmHg after fluid administration).
13. Patients with need for vasopressors.
14. Patients with altered consciousness (Glasgow Coma Scale <= 12 points.
15. Patients who have received NPPV or HFNC within the past 4 weeks prior to the informed consent, or are using NPPV or HFNC at home (more than 6 hours/day).
16. Patients with tracheostomy.
17. Patients who are pregnant.
18. Patients with cognitive impairment or mental disorder who are regarded as inadequate to evaluate for the study by the investigators.
19. Patients who have participated in the other study at the time of the informed consent, or will participate in the other study.
20. Any other cases who are regarded as inadequate for the study enrollment by the investigators.

Both

acute hypoxemic respiratory failure

This is a prospective, randomized parallel study for demonstrating superiority of noninvasive positive pressure ventilation (NPPV) compared to high-flow nasal cannula oxygen therapy (HFNC) in acute hypoxemic respiratory failure in terms of the term from randomization to meeting criteria for endotracheal intubation.

Term from randomization to meeting criteria for endotracheal intubation censored at 28 days.

1. Proportion of patients who required endotracheal intubation within 28 days after randomization.
2. Mortality at 28 days
3. In-hospital mortality
4. Ventilator-free days
5. Change of oxygenation (PaO2/FIO2)
6. Arterial blood gas analysis
7. Duration of need for any respiratory support
8. Duration of hospital stay for respiratory illness
9. Adverse events
10. Need for Continuous sedation (Drug, dose, duration)

+81-78-382-6669

Jan. 31, 2019

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