Clinical trial NCT02465125: The Transfusion Triggers in Vascular Surgery Trial
Official title: The Transfusion Triggers in Vascular Surgery Trial: Two Different Transfusion Triggers for Postoperative Haemoglobin Separation and Adherence to Transfusion Strategies in Vascular Surgery: a Randomised Clinical Feasibility Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Atherosclerosis
Anemia
Aortic Aneurysm, Abdominal
Arterial Occlusive Diseases
Lead sponsor: Naestved Hospital
Sponsor class: OTHER
Collaborators: name: Copenhagen Trial Unit, Center for Clinical Intervention Research
name: Research Unit, Naestved, Region Zealand, Denmark.
First posted: 2015-06-08
Enrollment: 58
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Mean Post-operative hemoglobin (longitudinal outcome)
timeFrame: Day 0 - 15
Secondary outcomes:
measure: Units of red blood cells transfused (count data)
timeFrame: 30 days after operation
measure: Recruitment rate with 95% confidence interval
timeFrame: Day -1 (day before operation)
measure: Protocol suspension
timeFrame: 30 days after operation
measure: Protocol adherence
timeFrame: 30 days after operation
measure: Intraoperative tissue oxygenation
timeFrame: Participants will be monitored during their stay at the operation theatre, an expected average of 3 hours
measure: Changes in coagulation competence measured by rotational thromboelastometry (ROTEM)
timeFrame: An expected average time frame of 3 hours
measure: Severe adverse events
timeFrame: 30 days after operation
measure: Explorative Outcomes
timeFrame: 90 days after operation
Other outcomes:
Locations:
city: Slagelse
country: Denmark
facility: Slagelse Hospital
state: Region Zealand
Study officials:
affiliation: Slagelse Hospital
name: Anders Møller, Resident
role: PRINCIPAL_INVESTIGATOR
References:
citation: Carson JL, Stanworth SJ, Dennis JA, Trivella M, Roubinian N, Fergusson DA, Triulzi D, Doree C, Hebert PC. Transfusion thresholds for guiding red blood cell transfusion. Cochrane Database Syst Rev. 2021 Dec 21;12(12):CD002042. doi: 10.1002/14651858.CD002042.pub5.
citation: Moller A, Nielsen HB, Wetterslev J, Pedersen OB, Hellemann D, Winkel P, Marcussen KV, Ramsing BGU, Mortensen A, Jakobsen JC, Shahidi S. Low vs high hemoglobin trigger for transfusion in vascular surgery: a randomized clinical feasibility trial. Blood. 2019 Jun 20;133(25):2639-2650. doi: 10.1182/blood-2018-10-877530. Epub 2019 Mar 11.