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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03643939
Recruitment Status : Recruiting
First Posted : August 23, 2018
Last Update Posted : March 4, 2022
Sponsor:
Collaborators:
Ministry of Health, Brazil
Berry Consultants
Information provided by (Responsible Party):
Hospital do Coracao

Brief Summary:

RENOVATE study aims to investigate if the respiratory support device called High-Flow Nasal Oxygen Cannula (HFNC) acts similarly (non-inferior) to another respiratory support device called Non-Invasive positive-pressure Ventilation (NIPPV) in preventing endotracheal intubation in adult patients with Acute Respiratory Failure (ARF) from different causes. HFNC is a somewhat new method of respiratory support in adults that has been used in neonatal ARF for some years. The reason this study is necessary is that, even though NIPPV has been demonstrated to prevent endotracheal intubation (and its associated complications) in a broad range of ARF patients, HFNC has been proposed to have the same beneficial effect of NIPPV while being easier tolerated, allowing patients to talk, eat and drink through mouth while on HFNC. RENOVATE will recruit between 800 to 2000 patients (adaptive design) with different types of ARF in Brazil. Patients will be randomized to HFNC or NIPPV and the rate of endotracheal intubation will be compared between groups as well as other parameters such as vital status and other health care related complications.

[IMPORTANT NOTE] On April 13, 2021, on the first interim analysis, the DSMB recommended the interruption of the immunocompromised hypoxemic ARF subgroup.


Condition or disease Intervention/treatment Phase
Respiratory Insufficiency Respiratory Failure Device: High Flow Nasal Catheter Device: Noninvasive ventilation Not Applicable

Detailed Description:

RENOVATE will investigate if High-Flow Nasal Oxygen Cannula (HFNC) is non-inferior to Non-Invasive positive-pressure Ventilation (NIPPV) in preventing endotracheal intubation or death in adult patients with Acute Respiratory Failure (ARF) from different causes in 7 days. HFNC is a somewhat new method of respiratory support in adults that has been used in neonatal ARF for some years. Even though NIPPV has been demonstrated to prevent endotracheal intubation (and its associated complications) in a broad range of ARF patients, HFNC may have beneficial effect over NIPPV because it is easier to be tolerated, allowing patients to talk, eat and drink through mouth while on therapy. RENOVATE will recruit between 800 to 2000 patients (adaptive design) with different types of ARF in Brazil. The main hypothesis is that HFNC is non inferior to NIPPV in reducing intubation rate or death within 7 days. However, as an adaptive study, this non inferiority hypothesis may change to superiority if gathered data during the study is promissing in the interim analysis. Therefore, sample size may increase to 2000 participants. Patients will be randomized to HFNC or NIPPV and the rate of endotracheal intubation will be compared between groups as well as other parameters such as vital status and other health care related complications.

[IMPORTANT NOTE] On April 13, 2021, on the first interim analysis, the DSMB recommended the interruption of the immunocompromised hypoxemic ARF subgroup.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Adaptive, non-inferiority randomized, open-label, controled clinical trial
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: RandomizEd Adaptive Trial of High-Flow Nasal Oxygen Cannula Compared to Non-Invasive Ventilation for AcuTE Respiratory Failure
Actual Study Start Date : November 1, 2019
Estimated Primary Completion Date : July 30, 2022
Estimated Study Completion Date : August 1, 2022


Arm Intervention/treatment
Experimental: High Flow Nasal Catheter
The HFNC (AIRVO2 Fisher & Paykel, Auckland, New Zealand) consists of an apparatus that allows adjustable FiO2 from 21 to 100% and delivers flow up to 60 L/ min.
Device: High Flow Nasal Catheter

HFNC will deliver through AIRVO2. FiO2 from 21 to 100% and heated humidified gas flow up to 60 l / min with temperature of the circuit maintained at 37 degrees.

Oxygen flow will be offered through a humidified nasal catheter. Flow and FiO2 will be titrated according to the protocol to maximize patient´s comfort and SpO2.

Other Names:
  • Optiflow
  • Airvo
  • trans-nasal insufflation
  • Nasal High Flow
  • High Flow Nasal Cannula
  • nasal cannula with high-flow oxygen

Active Comparator: Non-invasive positive pressure ventilation
NIPPV will be performed using the devices available on centers. Both a dedicated NIPPV device or invasive mechanical ventilator with NIPPV mode are accepted. The interface should be a oronasal or full face mask.
Device: Noninvasive ventilation
NIPPV will be performed using a facial mask (either oronasal or full face). NIPPV will deliver pressures and FiO2 tailored to specific ARF subgroups, according to the protocol. Adjustments of the inspiratory pressure (IPAP) and expiratory pressure (EPAP) and FiO2 according to protocol
Other Names:
  • BiPAP
  • Non-invasive ventilation
  • Noninvasive positive pressure ventilation




Primary Outcome Measures :
  1. Endotracheal intubation rate or death [ Time Frame: in 7 days ]
    proportion of endotracheal intubation or death


Secondary Outcome Measures :
  1. Mortality [ Time Frame: in 28 days ]
    Death

  2. Mortality [ Time Frame: in 90 days ]
    Death

  3. ICU free days [ Time Frame: in 28 days ]
    Days out of ICU

  4. IMV free days [ Time Frame: in 28 days ]
    Days without IMV inside of ICU after 48 hours of being extubated


Other Outcome Measures:
  1. Length of hospital stay [ Time Frame: in 90 days ]
    Time in hospital in days

  2. Length of ICU stay [ Time Frame: in 90 days ]
    Time in the ICU in days

  3. Vasopressor free days [ Time Frame: in 28 days ]
    Days without use of vasopressor inside of ICU

  4. Proportion of patients who received do-not-intubate-order [ Time Frame: in 7 days ]
    Proportion of patients that received DNI order after randomization was done

  5. Patient confort score [ Time Frame: 7 days ]
    Visual scale varying from 0 (no disconfort) to 100 (maximal disconfort)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

[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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03643939


Contacts
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Contact: Israel Maia, MD +55 11 30536611 ext 8209 israels.maia@gmail.com
Contact: Leticia Kawano-Dourado, MD +55 11 30536611 ext 8209 ldourado@hcor.com.br

Locations
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Brazil
Hospital do Coracao Recruiting
São Paulo, Brazil, 05435000
Contact: Marcelo Romano, MD         
Contact: Luzia Taniguchi, MSc         
Sponsors and Collaborators
Hospital do Coracao
Ministry of Health, Brazil
Berry Consultants
Investigators
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Study Chair: Alexandre B Cavalcanti, MD Research Institute - Hospital do Coracao, Sao Paulo, Brazil
Principal Investigator: Israel Maia, MD Research Institute - Hospital do Coracao, Sao Paulo, Brazil
Principal Investigator: Leticia Kawano-Dourado, MD Research Institute - Hospital do Coracao, Sao Paulo, Brazil
Study Chair: Laurent Brochard, MD St. Michael's Hospital (Toronto, Canada)
Study Chair: Carlos R Carvalho, MD Pulmonary Division University of Sao Paulo, Sao Paulo, Brazil
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Responsible Party: Hospital do Coracao
ClinicalTrials.gov Identifier: NCT03643939    
Other Study ID Numbers: RENOVATEmain_2018_08
First Posted: August 23, 2018    Key Record Dates
Last Update Posted: March 4, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hospital do Coracao:
respiratory insufficiency
respiratory failure
non-invasive ventilation
high flow nasal cannula
nasal high flow
trans-nasal insufflation
NIV
HFNC
Additional relevant MeSH terms:
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Respiratory Insufficiency
Respiration Disorders
Respiratory Tract Diseases