Low Tidal Volume Ventilation With Hyperoxia Avoidance During Cardiopulmonary Bypass (The FOCUS Trial)

The eFfect of cOntinuous Low Tidal Volume Ventilation With Hyperoxia Avoidance During CardiopUlmonary Bypass "FOCUS" Trial Blood Samples

This is a multi-institutional study (CCF, UPMC, OSU) evaluating different ventilation strategies during cardiopulmonary bypass on mortality and postoperative pulmonary complications, with sub-study investigating 8-iso-prostaglandin F2a and sRAGE levels.

Study Overview

• Status: Active, not recruiting
• Conditions: Cardiac Surgery
• Intervention / Treatment: Other: Continuous low-tidal volume ventilation with using FiO2 of 0.21; Other: Continuous low tidal volume ventilation with using FiO2 of 1.0; Other: Apnea During CPB

Detailed Description

The investigators will evaluate the effect of low tidal volume with varying FiO2 fractions during cardiopulmonary bypass on postoperative mortality and pulmonary complications. This will be a prospective, pragmatic, cluster randomized trial including all eligible adult cardiac surgical patients requiring cardiopulmonary bypass. Each week, all operating rooms will be randomized to one of three possible ventilation strategies during the period of cardiopulmonary bypass: 1) continuous low tidal volume ventilation with inspired oxygen fraction at 1.0, 2) continuous low tidal volume ventilation with inspired oxygen fraction at 0.21, and 3) no ventilation (apnea). The investigators will anticipate increase in plasma sRAGE and 8-iso-prostaglandin F2a levels in all three groups of patients during CPB with the highest levels immediately after cross-clamp release. The investigators will anticipate significant difference with at least 25% lower sRAGE levels in this group. The sub-study will also provide preliminary data on the behavior of the 8-iso-prostaglandin F2a which will be useful in further investigation of other targeted interventions to reduce ischemia-reperfusion injury to the lung during routine cardiac surgical operations.

• Study Type: Interventional
• Enrollment (Estimated): 5502
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• >18 years of age
• Male and female patients undergoing elective cardiac surgeries requiring cardiopulmonary bypass.

Exclusion Criteria:

Emergency surgeries, surgeries requiring lung isolation and one-lung ventilation (OLV), heart or lung transplants, and mechanical circulatory support device implantation pulmonary thrombendarterectomies.

• Surgeries requiring one-lung ventilation will be excluded because of the inability to employ study intervention and the differential treatment of the lungs likely confounding any potential effect from the planned intervention.
• Lung transplant surgeries will be excluded for similar reasons as well as other confounding effects affecting the primary composite outcome.
• Heart transplants and mechanical circulatory support device implantation surgeries will be excluded because these patients already receive intervention as part of the institutional protocol at the primary study site.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Continuous low-tidal volume ventilation with using FiO2 of 0.21; The investigator will investigate the effect of continuous low tidal volume ventilation with hyperoxia avoidance (using FiO2 of 0.21) on PPCs and 30-day mortality compared to low-tidal volume ventilation (with FiO2 of 0.21) or apnea during CPB, and during the sub-study.	Other: Continuous low-tidal volume ventilation with using FiO2 of 0.21; The continuous low-tidal volume ventilation with using FiO2 of 0.21 will be defined as the tidal volume of 3 mL/kg IBW (up to maximum 200 mL), 0.21 of FiO2, respiratory rate of 5 per minute, and PEEP 5 cm H20). A recruitment maneuver with 30 cm H2O for 10 seconds will be performed before starting the selected ventilation mode in all patients. During the sub-study extra blood samples will be drawn before and after CPB.
Active Comparator: Continuous low tidal volume ventilation with using FiO2 of 1.0; The investigator will investigate the effect of low tidal volume lung ventilation with hyperoxia avoidance (FiO2 of 0.21) on PPCs and mortality compared to hyperoxic low-tidal volume ventilation (with FiO2 of 1.0) or apnea during CPB, and during the sub-study.	Other: Continuous low tidal volume ventilation with using FiO2 of 1.0; The continuous low-tidal volume ventilation with using FiO2 of 1.0 will be defined as the tidal volume of 3 mL/kg IBW (up to maximum 200 mL), 1.0 of FiO2, respiratory rate of 5 per minute, and PEEP 5 cm H20). A recruitment maneuver with 30 cm H2O for 10 seconds will be performed before starting the selected ventilation mode in all patients. During the sub-study extra blood samples will be drawn before and after CPB.
Active Comparator: Apnea; The investigator will investigate the effect of apnea during on PPCs and mortality compared to hyperoxic low-tidal volume ventilation (with FiO2 of 1.0) or hyperoxia avoidance (FiO2 of 0.21) during CPB, and during the sub-study..	Other: Apnea During CPB; There will be no ventilation used. But, during the sub-study part of the Apnea CPB extra blood samples will be drawn before and after CPB.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of Composite including STS 30 day Mortality and postoperative pulmonary complications	Composite including STS 30-day mortality and postoperative pulmonary complications defined a early respiratory failure defined as PaO2/FiO2 ratio<200 mmHg at any time within the first 24 hours of ICU admission, postoperative reintubation during the hospital stay, prolonged ventilation, pneumonia, pleural effusion requiring drainage, pneumothorax requiring intervention, and readmission due to: pleural effusion requiring intervention, or pneumonia.	Within 30 days of surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CPB time	Duration of cardiopulmonary bypass (STS defined)	During surgery
ICU LOS	ICU length of stay (STS defined)	Within 30 days of surgery
Early respiratory failure - PaO2/FiO2 ratio < 200 mmHg at any time within the first 24 hours of ICU admission	PaO2/FiO2 ratio < 200 mmHg at any time within the first 24 hours of ICU admission	24 hours
Hospital LOS	Hospital length of stay (STS defined)	Within 30 days of surgery
Reintubation	Reintubation (STS defined)	Within 30 days of surgery
Need for tracheostomy	Need for tracheostomy (STS defined)	Within 30 days of surgery
Pleural effusion requiring drainage	Pleural effusion requiring drainage (STS defined)	Within 30 days of surgery
Pneumonia	Pneumonia (STS defined)	Within 30 days of surgery
Readmission	Readmission due to respiratory complication or need for thoracentesis and chest tube insertion (STS defined)	within 30 days of surgery
30-day mortality	STS defined in hospital mortality	Within 30 days of surgery

Collaborators and Investigators

• Sponsor: The Cleveland Clinic
• Collaborators: Ohio State University; University of Pittsburgh Medical Center; Society of Cardiovascular Anesthesiologists
• Investigators: Principal Investigator: Marta Kelava, MD, The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): March 30, 2027

Study Registration Dates

• First Submitted: July 20, 2021
• First Submitted That Met QC Criteria: July 20, 2021
• First Posted (Actual): July 27, 2021

Study Record Updates

• Last Update Posted (Actual): December 30, 2025
• Last Update Submitted That Met QC Criteria: December 22, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Respiratory; Hyperoxia
• Other Study ID Numbers: 21-447

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No