Supplemental Oxygen - Effect on Occurrence of Subsequent Cancer After Abdominal Surgery (Follow-up of the PROXI Trial) (PROXI)

Perioperative Inspiratory Oxygen Fraction - Effect on Occurrence of Subsequent Cancer After Abdominal Surgery (Follow-up of the PROXI Trial)

Aim: to investigate the effect of a high inspiratory oxygen fraction (FiO2) given during and after laparotomy procedures on occurrence of a subsequent, new or recurrent, cancer diagnosis at a long-term follow-up.

Background: A high inspiratory oxygen fraction (FiO2 = 0.80) has been linked to prevention of surgical site infection, but the Danish randomized clinical multicenter trial, the PROXI trial, found no difference in frequency of surgical site infection. In fact, long-term mortality was significantly increased with a hazards ratio of 1.30 in patients receiving 80% oxygen, and this appeared to be statistically significant in patients undergoing cancer surgery, but not in non-cancer patients.

At this point, no convincing mechanism explains the observed increased mortality after hyperoxia, as the long-term pathophysiological effects of oxygen are not fully understood.

Primary hypothesis of this follow-up study of the PROXI trial: Use of 80% oxygen increase the frequency of patients with a subsequent, new or recurrent, cancer.

Study Overview

• Status: Completed
• Conditions: Laparotomy
• Intervention / Treatment: Drug: Oxygen

• Study Type: Observational
• Enrollment (Actual): 1386

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, DK-2100
    • Dept. of Anesthesia, HOC, Copenhagen University Hospital, Rigshospitalet

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Participants in the PROXI trial

Description

Inclusion Criteria:

• Age 18 years or older.
• Laparotomy, acute or elective. In case of gynaecological surgery only if malignancy is suspected (defined as risk of ovarian malignancy index >200 or a specimen with atypical or neoplastic cells).

Exclusion Criteria:

• Other surgery within 30 days (except surgery in local anaesthesia).
• Chemotherapy within 3 months.
• Inability to give informed consent.
• Inability to keep oxygen saturation above 90% without supplemental oxygen (measured preoperatively by pulse oximetry).

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
80% oxygen group	Drug: Oxygen; During and 2 hrs after surgery
30% oxygen group	Drug: Oxygen; During and 2 hrs after surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Frequency of patients with the composite outcome measure of either a subsequent, new or recurrent, cancer registration or a new histological specimen showing any neoplasm	36-60 months after randomization

Secondary Outcome Measures

Outcome Measure	Time Frame
Frequency of patients with subsequent, new or recurrent, cancer registration at the Danish Cancer Registry	15-39 months after randomization
Frequency of patients with new histological specimen in the Danish Patobank showing any neoplasm	36-60 months after randomization
Frequency of patients with new histological specimen in the Danish Patobank showing neoplasm of a histological type not previously diagnosed	36-60 months after randomization
Frequency of patients with cancer as diagnosis code at a readmission	36-60 months after randomization
Frequency of patients with cancer as primary diagnosis code at a readmission	36-60 months after randomization
Duration of cancer-free survival, as assessed by Kaplan-Meier statistics	36-60 months after randomization

Other Outcome Measures

Outcome Measure	Time Frame
Type of new cancer registration	15-39 months after randomization
Histological type of new cancer specimen	36-60 months after randomization
Cause of death	15-39 months after randomization

Collaborators and Investigators

• Sponsor: Lars S. Rasmussen
• Investigators: Principal Investigator: Christian S Meyhoff, MD, PhD, Rigshospitalet, Denmark

Publications and helpful links

General Publications

• Meyhoff CS, Wetterslev J, Jorgensen LN, Henneberg SW, Hogdall C, Lundvall L, Svendsen PE, Mollerup H, Lunn TH, Simonsen I, Martinsen KR, Pulawska T, Bundgaard L, Bugge L, Hansen EG, Riber C, Gocht-Jensen P, Walker LR, Bendtsen A, Johansson G, Skovgaard N, Helto K, Poukinski A, Korshin A, Walli A, Bulut M, Carlsson PS, Rodt SA, Lundbech LB, Rask H, Buch N, Perdawid SK, Reza J, Jensen KV, Carlsen CG, Jensen FS, Rasmussen LS; PROXI Trial Group. Effect of high perioperative oxygen fraction on surgical site infection and pulmonary complications after abdominal surgery: the PROXI randomized clinical trial. JAMA. 2009 Oct 14;302(14):1543-50. doi: 10.1001/jama.2009.1452.
• Meyhoff CS, Wetterslev J, Jorgensen LN, Henneberg SW, Simonsen I, Pulawska T, Walker LR, Skovgaard N, Helto K, Gocht-Jensen P, Carlsson PS, Rask H, Karim S, Carlsen CG, Jensen FS, Rasmussen LS; PROXI Trial Group. Perioperative oxygen fraction - effect on surgical site infection and pulmonary complications after abdominal surgery: a randomized clinical trial. Rationale and design of the PROXI-Trial. Trials. 2008 Oct 22;9:58. doi: 10.1186/1745-6215-9-58.
• Meyhoff CS, Jorgensen LN, Wetterslev J, Siersma VD, Rasmussen LS; PROXI Trial Group. Risk of new or recurrent cancer after a high perioperative inspiratory oxygen fraction during abdominal surgery. Br J Anaesth. 2014 Jul;113 Suppl 1:i74-i81. doi: 10.1093/bja/aeu110. Epub 2014 May 23.

Study record dates

Study Major Dates

• Study Start: October 1, 2006
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: November 5, 2012
• First Submitted That Met QC Criteria: November 5, 2012
• First Posted (Estimated): November 7, 2012

Study Record Updates

• Last Update Posted (Actual): November 18, 2024
• Last Update Submitted That Met QC Criteria: November 14, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: 2006-001710-32-follow-up; GCP-2006-101 (Other Identifier: Danish GCP-unit); KF 02 306766 (Other Identifier: Ethics committee)