High Flow Nasal Cannula in Severe Sepsis (OPTISEPSIS)

January 12, 2021 updated by: Rafael Fernandez, Althaia Xarxa Assistencial Universitària de Manresa

High Flow Nasal Cannula Therapy as an Adjuvant in the Treatment of Severe Sepsis. A Multicenter Parallel-group Randomized Clinical Trial

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Severe sepsis is a syndrome associated with severe infections with a high morbidity and mortality. In its most severe form, septic shock still leads to an in-hospital mortality of up to 50%. The pathophysiology of severe sepsis / septic shock includes increased work of breathing to compensate for tissue hypoperfusion-induced metabolic acidosis. This exaggerated work of breathing requires increased consumption of oxygen by respiratory muscles, which calls for a greater percentage of the already insufficient cardiac output, which can aggravate tissue hypoperfusion.

In the last decade, high flow nasal cannula (HFNC) appeared as an alternative ventilatory support intermediate between conventional oxygen and mechanical ventilation. Among others (3-7), the investigators have also demonstrated their effectiveness in patients with respiratory failure of different etiologies (8-11). Patients treated with HFNC quickly show a reduction of respiratory rate and respiratory work, associated with an improvement of the functional residual capacity and gas exchange. The absence of significant side effects and low cost makes HFNC especially attractive as adjunctive medical treatment in severe sepsis.

Then, the hypothesis is that in patients with severe sepsis, high flow nasal cannula (HFNC) therapy could reduce work of breathing, which would allow a redistribution of cardiac output from the respiratory muscles to other organs, improving peripheral perfusion with minor injury of organs at distance, less multiorgan failure and improved survival. Therefore, the aim of this study is to evaluate the efficacy of HFNC for improving sixty-day survival in patients with severe sepsis. This study will also provide a detailed evaluation of the HFNC's effects on the need for vital support (mechanical ventilation, dialysis, vasoactive drugs) and physiological parameters (acidosis, clearance of lactate, SvO2 and SOFA).

DESIGN Prospective, multicenter, randomized, controlled trial in 592 patients with severe sepsis admitted into a network of 18 ICUs from university and community hospitals in Spain to define the role of high flow oxygen therapy, with one experimental arm that will receive high flow oxygen therapy and a control arm that will receive conventional oxygen therapy if required.

Patients who consent will be randomized in a 1:1 ratio to receive HFNC or conventional treatment, which consists of adding oxygen on nasal prongs or Venturi mask only if hypoxemia is detected as SpO2 < 92% by pulse oximetry.

STUDY ARMS

  1. HFNC therapy (experimental group) Treatment with HFNC (Airvo2® Fisher & Paykel, and AquaNASE® Armstrong Medical) will begin with high flow (50 L/min), high temperature and humidity and oxygen concentration 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.

    In HFNC patients we propose an extra caution to avoid delaying a mechanical ventilation that would be beneficial. To do this, the ROX index (ROX = SpO2/FiO2/respiratory rate) will be calculated and if it is < 5, it is recommended to assess mechanical ventilatory support, either invasive or non-invasive.

  2. Conventional therapy (control group) 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.

Study Type

Interventional

Enrollment (Actual)

39

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
    • Barcelona
      • Manresa, Barcelona, Spain, 08242
        • ICU. Fundacio Althaia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 99 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: High-Flow nasal cannula (HFNC)

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)
The patient will receive HFNC adjusted for SatO2 > 92% and with, at least, 30 liters of total flow.
Other Names:
  • Conventional therapy
No Intervention: Conventional therapy

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mortality
Time Frame: 60 day
60-day survival after enrollment
60 day

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mechanical ventilation support
Time Frame: up to 60-days
Institution of mechanical ventilation (either invasive or noninvasive)
up to 60-days
Dialysis support
Time Frame: up to 60-days
Institution of dialysis
up to 60-days
Vasoactive drugs tappering
Time Frame: up to 60-days
Daily dose of vasoactive drugs until stopping
up to 60-days
Sequential Organ Failure Assessment
Time Frame: up to 60-days
Daily Sequential Organ Failure Assessment score. The organs scored are respiratory, cardiovascular, neurologic, hematologic, renal, and liver. Each organ is scored as 0 (best) to 4 (worse) and the total score is the sum of each component.
up to 60-days
Acidosis improvement
Time Frame: up to 60-days
Hours until the ph becomes normal
up to 60-days
Central Venous Oxygen Saturation (SatVO2)
Time Frame: up to 60-days
Hours until the SatVO2 < 65%
up to 60-days
Lactate clearance
Time Frame: up to 60-days
Hours until lactate < 3 mmol/l
up to 60-days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Althaia Xarxa Assistencial Universitària de Manresa

Investigators

  • Principal Investigator: Rafael Fernandez, PhD, Fundació Althaïa

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 8, 2018

Primary Completion (Actual)

November 28, 2020

Study Completion (Actual)

December 28, 2020

Study Registration Dates

First Submitted

October 25, 2017

First Submitted That Met QC Criteria

November 6, 2017

First Posted (Actual)

November 7, 2017

Study Record Updates

Last Update Posted (Actual)

January 14, 2021

Last Update Submitted That Met QC Criteria

January 12, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CEI17/54

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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