High Flow Nasal Cannula in Severe Sepsis

NCT03334227 | Terminated DMC

• 1 other identifier: CEI17/54
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

Severe sepsis leads a high morbidity and mortality by causing organ damage at distance. The treatment relies on early antibiotic therapy and hemodynamic resuscitation. Hypothesis: high flow nasal cannula (HFNC) could reduce work of breathing and improve the outcome of patients with severe sepsis and peripheral perfusion. Objective: the aim of this study is to evaluate the efficacy of HFNC for improving sixty-day survival in patients with severe sepsis. Design: multicenter parallel-group randomized clinical trial. Method: 592 adult patients with a diagnosis of severe sepsis in the first 12 hours of admission in the Emergency Room will be randomly assigned to an experimental or control group. In the experimental group, HFNC will be administered until the resolution of sepsis or until required mechanical ventilation, either invasive or non-invasive. In the Control group, conventional oxygen will be administered, if required. Sixty-day survival will be the primary outcome. The study is powered to demonstrate an improvement in survival from 70% in control group up to 80% in the HFNC group. The secondary outcomes will be reducing the need for vital support (mechanical ventilation, dialysis, vasoactive drugs) and physiological (acidosis, clearance of lactate, SvO2 and SOFA). Statistical analysis: Kaplan-Meier curves and Cox proportional hazard models will be calculated for all-cause sixty-day survival. If the results are conclusive, they will have immediate application in medical practice.

Conditions

Severe Sepsis

Keywords

High-Flow Nasal Cannula; Severe Sepsis; qSOFA

Outcome Measures

Primary Outcomes (1)

• Mortality

  60-day survival after enrollment

  60 day

Secondary Outcomes (7)

• Mechanical ventilation support

  up to 60-days

• Dialysis support

  up to 60-days

• Vasoactive drugs tappering

  up to 60-days

• Sequential Organ Failure Assessment

  up to 60-days

• Acidosis improvement

  up to 60-days

Study Arms (2)

High-Flow nasal cannula (HFNC)

EXPERIMENTAL

Treatment with HFNC will be adjusted for SpO2 \>92%, even with FiO2 of 0.21, if needed. The rationale for this HFNC dosage is that minute ventilation can be already reduced with 30 L/min, but functional residual capacity and oxygenation maximally improve at higher flow. On the contrary, flow \>50 L/min is uncomfortable for many patients. In the case of clinical intolerance, flow will be reduced to 40, 30 or 20 L/min. Yet it is not tolerated, HFNC will be stopped and patients will receive conventional oxygen if required, but will be evaluated as in the HFNC group by intention to treat.

Device: High-Flow nasal cannula (HFNC)

Conventional therapy

NO INTERVENTION

Patients assigned to the conventional treatment will receive the standard care given at hospital which consists of adding oxygen on nasal prongs or Venturi mask only if hypoxemia is suggested by SpO2 \< 92% by pulse oximetry. Target for oxygenation in both arms is SpO2 between 92% and 95%. SpO2 \>95% without oxygen supply is acceptable. On the contrary, SpO2 \<92% may be acceptable when needed for medical reasons, mainly chronic hypercapnic patients.

Interventions

High-Flow nasal cannula (HFNC) DEVICE

The patient will receive HFNC adjusted for SatO2 \> 92% and with, at least, 30 liters of total flow.

Also known as: Conventional therapy

High-Flow nasal cannula (HFNC)

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients \> 18 yr. with diagnostic criteria for severe sepsis, within 12 hours of admission in the Emergency Room, defined as hypotension after hemodynamic resuscitation, initial lactate \> 4, or persistence of organ dysfunction (oliguria \< 0.5 ml/kg/h, cyanosis, or altered consciousness).(qSOFA 1, 2 or 3)

You may not qualify if:

• Patients who require immediate ventilatory support both invasive and non-invasive, defined by severe hypoxemia (PaO2/FiO2 \< 150), severe tachypnea (40 x') with signs of respiratory fatigue or low level of consciousness (Glasgow \< 8).
• Patients with limitation of the therapeutic effort or orders of not CPR.
• Patients not susceptible to treatment with HFNC (facial trauma, tracheostomized, rejection of previous treatments with HFNC).
• Participation in other clinical trials that may affect survival.
• Home treatment with oxygen, CPAP or Non-invasive ventilation.

Sponsors & Collaborators

• Althaia Xarxa Assistencial Universitària de Manresa: lead

Study Sites (1)

ICU. Fundacio Althaia

Manresa, Barcelona, 08242, Spain

Location

Related Publications (9)

• Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb S, Beale RJ, Vincent JL, Moreno R; Surviving Sepsis Campaign Guidelines Committee including The Pediatric Subgroup. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013 Feb;39(2):165-228. doi: 10.1007/s00134-012-2769-8. Epub 2013 Jan 30.

  PMID: 23361625 RESULT

• Viires N, Sillye G, Aubier M, Rassidakis A, Roussos C. Regional blood flow distribution in dog during induced hypotension and low cardiac output. Spontaneous breathing versus artificial ventilation. J Clin Invest. 1983 Sep;72(3):935-47. doi: 10.1172/JCI111065.

  PMID: 6886012 RESULT

• Roca O, Riera J, Torres F, Masclans JR. High-flow oxygen therapy in acute respiratory failure. Respir Care. 2010 Apr;55(4):408-13.

  PMID: 20406507 RESULT

• Riera J, Perez P, Cortes J, Roca O, Masclans JR, Rello J. Effect of high-flow nasal cannula and body position on end-expiratory lung volume: a cohort study using electrical impedance tomography. Respir Care. 2013 Apr;58(4):589-96. doi: 10.4187/respcare.02086.

  PMID: 23050520 RESULT

• Stephan F, Barrucand B, Petit P, Rezaiguia-Delclaux S, Medard A, Delannoy B, Cosserant B, Flicoteaux G, Imbert A, Pilorge C, Berard L; BiPOP Study Group. High-Flow Nasal Oxygen vs Noninvasive Positive Airway Pressure in Hypoxemic Patients After Cardiothoracic Surgery: A Randomized Clinical Trial. JAMA. 2015 Jun 16;313(23):2331-9. doi: 10.1001/jama.2015.5213.

  PMID: 25980660 RESULT

• Frat JP, Thille AW, Mercat A, Girault C, Ragot S, Perbet S, Prat G, Boulain T, Morawiec E, Cottereau A, Devaquet J, Nseir S, Razazi K, Mira JP, Argaud L, Chakarian JC, Ricard JD, Wittebole X, Chevalier S, Herbland A, Fartoukh M, Constantin JM, Tonnelier JM, Pierrot M, Mathonnet A, Beduneau G, Deletage-Metreau C, Richard JC, Brochard L, Robert R; FLORALI Study Group; REVA Network. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med. 2015 Jun 4;372(23):2185-96. doi: 10.1056/NEJMoa1503326. Epub 2015 May 17.

  PMID: 25981908 RESULT

• Hernandez G, Vaquero C, Colinas L, Cuena R, Gonzalez P, Canabal A, Sanchez S, Rodriguez ML, Villasclaras A, Fernandez R. Effect of Postextubation High-Flow Nasal Cannula vs Noninvasive Ventilation on Reintubation and Postextubation Respiratory Failure in High-Risk Patients: A Randomized Clinical Trial. JAMA. 2016 Oct 18;316(15):1565-1574. doi: 10.1001/jama.2016.14194.

  PMID: 27706464 RESULT

• Hernandez G, Vaquero C, Gonzalez P, Subira C, Frutos-Vivar F, Rialp G, Laborda C, Colinas L, Cuena R, Fernandez R. Effect of Postextubation High-Flow Nasal Cannula vs Conventional Oxygen Therapy on Reintubation in Low-Risk Patients: A Randomized Clinical Trial. JAMA. 2016 Apr 5;315(13):1354-61. doi: 10.1001/jama.2016.2711.

  PMID: 26975498 RESULT

• Fernandez R, Subira C, Frutos-Vivar F, Rialp G, Laborda C, Masclans JR, Lesmes A, Panadero L, Hernandez G. High-flow nasal cannula to prevent postextubation respiratory failure in high-risk non-hypercapnic patients: a randomized multicenter trial. Ann Intensive Care. 2017 Dec;7(1):47. doi: 10.1186/s13613-017-0270-9. Epub 2017 May 2.

  PMID: 28466461 RESULT

MeSH Terms

Conditions

Sepsis

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Rafael Fernandez, PhD

  Fundacio Althaia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director. Critical Care Department

Model Details: Patients with severe sepsis will be randomized to recieve conventional oxygenotherapy if needed or high flow nasal cannula.

Study Record Dates

• First Submitted: October 25, 2017
• First Posted: November 7, 2017
• Study Start: January 8, 2018
• Primary Completion: November 28, 2020
• Study Completion: December 28, 2020
• Last Updated: January 14, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)