BACKGROUND

• Vascular surgical patients often receive red blood cell (RBC) transfusions in the peri-operative period
• RBC transfusion may lead to improved outcome but on the other hand the intervention may be harmful
• Danish Health and Medicines Authority recommends transfusion of RBC at hemoglobin below 5 mmol/L while local clinical guidelines recommend transfusion of RBC to maintain hemoglobin levels above 6 mmol/L
• A large randomized clinical trial is needed to evaluate the efficacy and safety of RBC transfusion in patients undergoing vascular surgery.
• A trial examining the effect of RBC transfusion on tissue oxygenation is used to test the trial-design and feasibility for a trial evaluating post-operative mortality and morbidity.

DESIGN Single-center, randomized, open-label trial including vascular surgical patients for peri-operative red blood cell (RBC) transfusion.

If the patient drops out of the trial, either at his/her own request or due to withdrawal from active therapy, the patient will be followed up in the intention-to-treat analyses.

PROTOCOL SUSPENSION

The patient can temporarily be suspended from the protocol in the following circumstances, if the clinician in charge finds indication for blood transfusions not adhering to the planned transfusion threshold:

• Uncontrollable bleeding, defined as loss of surgical hemostasis resulting in overt or imminent hemodynamic instability with insufficient tissue oxygenation and increasing lactate production OR
• Hypotension unresponsive to fluid replacement OR
• Decompensated heart failure OR
• Stroke, extremity- and intestinal ischaemia

SAMPLE SIZE With a total of 50 randomised patients, the trial is powered to

• Show difference in mean postoperative hemoglobin of 1.0 mmol/L. With a power of 95%, 5% significance and a standard deviation of 0.9 mmol/L.
• Show a difference in 2 units (600 mL) of RBC transfused based on a standard deviation of RBC transfusion volume of 717 mL, with a power of 80 % and 5% significance
• Produce a 97.5% confidence interval (CI) equal to the sample adherence prevalence plus or minus 8% when the true prevalence of adherence is hypothesized to be 90%
• Detect a difference in near infrared spectroscopy-determined tissue oxygenation (ScO2) of 6 % during surgery. With a power of 80%, 5% significance and a ScO2-standard deviation of 7%

TIME-LINE The first patient is expected to be randomized June 8th 2015, the last will be randomized March 31st 2016 and the trial database is expected to be closed ultimo June 2016. The main manuscript will be submitted shortly thereafter.

PROTOCOL AMENDMENTS

1. The Ethical Committee of Region Zealand has approved a protocol amendment of March 29th 2016 for permission of extending the trial period to the end of 2016.
2. On September 20th 2016 The Ethical Committee of Region Zealand approved a protocol amendment of September 16th 2016 for permission of extending the sample size to 58 patients and extending the trial period to June 31st 2017.

The 2nd amendment was submitted to compensate for an unexpected high rate of patients randomised postoperatively and thus to secure a sufficient sample size (n=44) for the primary outcome measure, postoperative Hb, and the secondary outcome measures NIRS and ROTEM.

Inclusion Criteria:

• Patients for planned open repair of the abdominal aorta or infrainguinal arterial bypass
• Hemoglobin < 6 mmol/L

Exclusion Criteria:

• Documented wish against transfusion
• Previous serious adverse reaction with blood products
• Unable to understand the benefits and risks of testing
• Previous participation in trial