Clinical trial NCT05550623: Pneumatic Tourniquet Versus no Tourniquet in Transfemoral Amputation
Official title: Pneumatic Tourniquet Versus no Tourniquet in Transfemoral Amputation - A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Amputation
Blood Loss
Keywords: Tourniquet
Major Lower Extremity Amputation
Transfemoral Amputation
Blood Loss
Lead sponsor: University of Southern Denmark
Sponsor class: OTHER
Collaborators: name: Odense University Hospital
First posted: 2022-09-22
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, prospective, two-arm, blinded trial. Superiority-design Allocation 1:1 Eligible patients will be randomized to transfemoral surgery with or without the application of a sterile pneumatic tourniquet.
Primary purpose: PREVENTION

Brief summary: Lower extremity amputation patients represent a frail group of patients with extensive comorbidity. The most common indication of amputation is ischemia, infection and concomitant ischemic pain due to underlying chronic disease, especially arteriosclerosis and diabetes.

Prolonged general anesthesia and surgery as well as increased blood loss may result in impaired patient safety. Previous studies have shown total blood loss approx. 1000 mL in transfemoral amputations (TFA). Substantial blood loss during surgery increases the risk of anemic complications and death for this already weakened patient group.

The aim of this randomized controlled trial is to improve patient safety by exploring the possibility of a more precautious surgical procedure for TFA. Hence, investigating the total blood loss and secondary differences in complications after TFA between patients operated with use of pneumatic tourniquet versus no tourniquet. Total blood loss is calculated via Nadlers approach. From a pilot series, sample size was calculated to 124, allocated 1:1 in two groups of 62 participants, to ensure detection of at least 200 mL difference in total blood loss.

The hypothesis is that use of tourniquet will decrease the total blood loss, the amount of blood transfusions, time of surgery and complications related to postoperative anemia without a higher rate of adverse events. The secondary and explorative outcomes are blood transfusions, intraoperative blood loss, length of stay, time of surgery, risk of readmission, risk of re-operation, risk of mortality, complications during admission, quality of life (QoL), prosthesis use and the prosthesis-specific survey Prothesis Evaluation Questionnaire (PEQ). QoL is measured with the validated questionnaire EQ-5D-5L preoperatively, and at 3, 6, and 12 months postoperatively.

The possibility to enhance patient safety is highly relevant, and this trial will aid in establishing evidence-based guidelines for TFA surgery.

Detailed description: Hypothesis The hypothesis is that the use of tourniquet in Transfemoral amputation (TFA) surgery will reduce the total blood loss, the intraoperative blood loss and the need for blood transfusion post-operatively and thereby improve patient safety.

Aim Primary to investigate total blood loss and secondary to investigate differences in complications after TFA surgery between patients operated with use of pneumatic tourniquet versus no tourniquet.

Trial design overview Design: Randomized, prospective, blinded, two-arm, single center trial. Superiority-design. Group 1: Transfemoral amputation performed with tourniquet application Group 2: Transfemoral amputation performed without tourniquet application Population: Patients with indication for primary transfemoral amputation (intact femoral bone). Period: Expected trial inclusion period is October 2022- September 2024. Place: Odense University Hospital (OUH), Odense, Denmark Sample size: 62 in each group, a total of 124 participants inclusive a 20 % buffer.

The flow of TFA patients in the department is approximately 100 patients annually and it will therefore be possible to include the calculated sample size in the time frame available for this trial.

Tourniquet: The tourniquet that is used at OUH is FastAir® distributed and imported by Universal Medical Supplies Aps. Universal Medical Supplies Aps is not a part of this protocol.

This trial is not conducted in collaboration with Universal Medical Supplies Aps. Universal Medical supplies Aps has no right to unpublished study data and is neither financially nor personally involved in this trial. None in the study group is related to Universal Medical Supplies ApS. MDR classification for FastAir® tourniquet: class I, non-invasive device for temporary use.

The FastAir® tourniquet has a CE-certificate. The FastAir® tourniquet will be used according to instructions for use. Tourniquet application for transfemoral amputation at OUH is not standard of care.

Randomizing and database Randomization is performed internet-based using REDCap Randomize, allocation 1:1. The randomization itself takes place in the period 4 weeks prior to surgery to immediately before surgery. The randomization is performed as a block randomization and will be stratified for age (\>70 years / ≤70 years) and hemoglobin value pre surgery (\>6mmol/L / ≤6 mmol/L). Two stratifies is acceptable for the calculated sample size.

Blinding Participants and staff not attendant in the room will be blinded. The use of tourniquet will not be visible in the patient records but recorded directly in the REDCap Database. A standard phrase to describe the surgical procedure will be used in the patient record. Deviations and adverse events will be described. Participants will be able to be informed by the procedure after 6 months.

Feasibility In a pilot study, feasibility of tourniquet application was assessed. The pilot-study was carried out in the department in May-July 2021. Placement of tourniquet for TFA surgery is generally possible in \>90%. The blood tests are not always drawn at third day post surgery, but this will be assessed in the new department algorithm for postoperative care for major lower extremity amputation patients, to ensure correct data collection in this study. The mean application time of the tourniquet was 12,15 minutes (5 minutes -21 minutes).

Sample Size From the pilot series there was observed a mean of 429 ml and standard deviation (SD) of 199 ml in 11 intervention procedures (with tourniquet) and a mean of 730 ml and SD of 446 ml in 12 control procedures (without tourniquet). The calculated blood loss in each group was normally distributed according to quantile-quantile plots (Appendix 1). It is assumed that a mean difference of 200 ml would be lower than any reasonable clinically important difference, and hence chose this as the difference for our sample size calculation.

From this,there was calculated the need of 49 participants in each group for a two-sample t-test fora superiority trial. To take into account for up to 20% drop-out (e.g. due to invalid data/protocol violation/intraoperative mortality/participant wish/investigator indication), it was decided to include 62 participants in each group (49/0,8=61,25). The sample size calculation was performed in Stata/IC 16.1with help from OPEN Statistics,OUH.

Screening log is performed on patients not included, to examine the cause of non-inclusion.

Patients that are not included in this study, no matter of cause, will be offered to participate in a concurrently prospective non-interventional cohort study where the main outcome is health related quality of life before and after surgery. These patients will only receive electronic surveys (in E-boks) regarding quality of life (EQ-5D), disease course, pain, mobility and daily life. This will serve as drop-out analysis. The same baseline data will be recorded on these patients. They will receive the department standard treatment.

Statistical analysis plan The investigators will report descriptive statistics of patient characteristic as mean and standard deviation (SD) for normally distributed, median and interquartile range (IQR) for non-normally distributed, and counts and proportions for categorical characteristics. The investigators will compare the primary outcome (calculated blood loss) by two-sample t-test with unequal variance and report mean and SD for each group as well as the mean difference with a 95% normal confidence interval (CI). The investigators will report the dichotomous secondary and exploratory outcomes as counts and proportions, compare these with chi-squared test (or Fisher's exact test, if any counts are below five) and report odds ratios with 95% CI from crude logistic regression. The investigators will report numerical secondary and exploratory outcomes either as means and SD and compare those by two-sample t-test, if deemed normally distributed by quantile-quantile plots, or otherwise, as medians and IQR and compared by Wilcoxon rank-sum test if not deemed normally distributed. All analyses will be carried out as a superiority design and as intention to treat analysis is performed for all included participants, and p-values below 0.05 will be considered statistically significant.

Eligibility criteria: Inclusion Criteria:

* Speak and understand Danish and able to give informed consent
* ≥18 years of age
* Indication for first transfemoral amputation (intact femur)

Exclusion Criteria:

* Bilateral amputation in same procedure
* Femoral amputation revision (non-intact femur)
* Malignant disease as main cause of amputation
* Not possible to place tourniquet correctly (surgeon assessment)
* Acute trauma
* Planned surgery with surgeon charged less than second year residents.

Primary outcomes:
measure: Total blood loss calculated using Nadler's approach
timeFrame: Day 1- Day3
Secondary outcomes:
measure: Blood transfusion
timeFrame: Day 1- Day 3
measure: Intraoperative blood loss
timeFrame: Day 1
measure: Length of stay
timeFrame: Day 1 - To discharge or date of death, whichever comes first, with a maxium of 52 weeks
measure: Complications during admission
timeFrame: Day 1 - To Discharge or date of death, whichever comes first, with a maxium of 52 weeks
measure: Risk of mortality ≤30 days
timeFrame: Day 1 - Day 30
measure: Risk of readmission ≤90 days
timeFrame: Day 1 - Day 90
measure: Risk of re-operation ≤30 days and ≤90 days
timeFrame: Day 1- Day 90
Other outcomes:
measure: Risk of re-operation ≤ 1 year
timeFrame: Day 1 - Day 365
measure: Risk of mortality ≤ 1 year
timeFrame: Day 1 - Day 365
measure: Prosthesis user ≤ 1 year
timeFrame: Day 1 - Day 365
measure: Quality of Life (EQ-D5)
timeFrame: Day 1 - Day 365
measure: Prosthesis Evaluation Questionnaire (PEQ)
timeFrame: Day 365
Locations:
city: Odense
country: Denmark
facility: Odense University Hospital
state: Funen
Study officials:
affiliation: Odense University Hospital
name: Martin Lindberg-Larsen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Brix ATH, Nymark T, Schmal H, Lindberg-Larsen M. Pneumatic tourniquet versus no tourniquet in transfemoral amputation - a study protocol for a randomized controlled trial. BMC Musculoskelet Disord. 2022 Dec 13;23(1):1088. doi: 10.1186/s12891-022-06000-6.