High-Flow Nasal Oxygen Cannula Compared to Non-Invasive Ventilation in Adult Patients With AcuTE Respiratory Failure (RENOVATE)

This is an interventional treatment trial for Respiratory Insufficiency focused on measuring respiratory insufficiency, respiratory failure, non-invasive ventilation, high flow nasal cannula, nasal high flow, trans-nasal insufflation, NIV, HFNC Read More

[IMPORTANT NOTE] On April 13th 2021, in the first interim analysis, the DSMB recommended for the interruption of the subgroup Immunocompromised De Novo Hypoxemic ARF due to futility.

Sequential adult patients 18 years of age or older admitted to the ICU or emergency department with acute onset respiratory distress suspected of having De Novo hypoxemic ARF (non-immunocompromised) , Immunocompromised De Novo hypoxemic ARF, COPD ARF, Cardiogenic acute pulmonary edema (APE).

Inclusion criteria for these 4 ARF subgroups are detailed below:

A. Inclusion Criteria for Non-Immunocompromised De Novo Hypoxemic ARF.

Patients must meet criteria 1, 2 and 3:

1. Hypoxemia evidenced by SpO2 <90% or PaO2 <60 mmHg in room air
2. Use of accessory muscles, paradoxical breathing, and/or thoracoabdominal asynchrony
3. RR> 25 per minute

B. Inclusion Criteria for Immunocompromised De Novo Hypoxemic ARF.

Patients must meet criteria 1, 2, 3 and 4:

1. Immunosuppression diagnosis:

   i. Use of Immunosuppressive drug or long-term [>3 months] or high-dose [>0.5 mg/kg/day] steroids ii. Solid organ transplantation iii. Extensive solid tumor or solid tumor requiring chemotherapy in the last 5 years iv. Hematological malignancy regardless of time since diagnosis and received treatments v. HIV infection vi. Primary immunodefiency

2. Hypoxemia evidenced by SpO2 <90% or PaO2 <60 mmHg in room air
3. Use of accessory muscles, paradoxical breathing, and/or thoracoabdominal asynchrony
4. RR> 25 per minute

C. Inclusion Criteria for COPD exacerbation:

Patients must meet criteria 1 or 2 and 3 and 4:

1. Previous Diagnosis of COPD based on GOLD guidelines
2. Strong clinical suspicion of COPD i. Smoker or ex-smoker or other CPOD related exposure ii. Presence of chronic dyspnea on exertion or chronic productive cough iii. Excluded other causes for the chronic symptoms (ex. pulmonary fibrosis, heart failure)
3. RR> 25 per minute or use of accessory muscles, paradoxical breathing, and/or thoracoabdominal asynchrony
4. ABG analysis with pH < 7,35 , paCO2> 45 mmHg

D. Inclusion Criteria for ARF secondary to Cardiogenic APE.

Patients must meet criteria numbers 1, 2 and 3:

1. Diagnosis of Cardiogenic Acute Pulmonary Edema (Nava, 2003):

   i. Dyspnea of sudden onset ii. Widespread rales with or without third heart sound 1 iii. Absent history of pulmonary aspiration, infection or previous history of pulmonary fibrosis iv. Pulmonary edema as the main clinical hypothesis v. Previous heart failure clinical history or acute coronary syndrome vi. If chest X-ray is already available at randomization, it must be suggestive of bilateral pulmonary edema

2. RR > 25 per minute
3. SpO2 < 95%

Exclusion Criteria for all subgroups of ARF

1. Indication of emergency ETI:

   • Prolonged respiratory pauses
   • Cardiorespiratory arrest
   • Glasgow ≤12
   • HR < 50 bpm with decreased level of consciousness
   • pH < 7.15 irrespective of the cause
2. Psychomotor agitation that prevents adequate medical / nursing care requiring heavy sedation
3. Persistent hemodynamic instability with MAP <65 mmHg, SBP <90 mmHg after adequate volume resuscitation or requiring norepinephrine> 0.3 microg / kg / min or equivalent.
4. Contraindications to non-invasive ventilation: face deformities or traumas, recent esophageal surgery, hypersecretion, vomiting with aspiration risk
5. Presence of pneumothorax or extensive pleural effusion
6. Severe arrhythmias at risk of hemodynamic instability
7. Thoracic trauma understood as the main cause of ARF
8. Asthma attack
9. Pregnancy
10. Cardiogenic Shock
11. Acute Coronary Syndromes with plans to undergo coronary angiography within 24 hs
12. ARF after orotracheal extubation (up to 72 hours after extubation)
13. Post-surgical ARF (surgery within 72 hours)
14. Hypercapnic ARF due to neuromuscular disease or chest deformities
15. Patients on exclusive palliative care
16. Do Not Intubate order (DNI)
17. Chronic pulmonary disease except COPD
18. Use of more than 6 hours of NIPPV before randomization if hypoxemic ARF in the non-immunosuppressed, in the immunosuppressed hypoxemic, or if exacerbated COPD
19. Use of NIPPV before randomization in the cardiogenic acute pulmonary edema