The ALOFT Pilot Trial

Study Overview
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Brief Summary
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The ALOFT Pilot Trial will evaluate three pragmatic elements (recruitment, adherence, and follow-up) of neuraxial versus general anesthesia for lower limb revascularization surgery that are necessary to support a successful, large-scale evaluation. We will concurrently use implementation science methodology to further refine processes for the larger trial. The future full ALOFT trial will be designed to evaluate the comparative effectiveness of two different anesthesia types for improving outcomes.

Detailed Description
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Background: Despite promising evidence suggesting benefit from neuraxial anesthesia for lower limb revascularization surgery, our data demonstrate that use of neuraxial anesthesia varies 6-fold between Canadian hospitals and is decreasing over time. Currently available evidence is largely observational. Only data from a multicenter, randomized trial of anesthesia type for lower limb revascularization surgery, powered for patient-reported outcomes and designed with patient and knowledge user partners, will provide the high-certainty evidence of the possible benefits of neuraxial anesthesia. Therefore, we are designing the Anesthesia for Lower limb revascularization to Optimize Functional ouTcomes (ALOFT) Trial to address this important question. Prior to conducting this full trial, the feasibility of the trial protocol must be demonstrated using a multicenter pilot design. Overarching Aim: The ALOFT Pilot Trial will evaluate three pragmatic elements (recruitment, adherence, and follow-up) of neuraxial versus general anesthesia for lower limb revascularization surgery that are necessary to support a successful, large-scale evaluation. Methods: Design, setting and participants: The ALOFT Pilot Trial is an assessor blinded, multicenter, individual patient, parallel-arm randomized controlled trial. People => 18 years with a planned lower limb revascularization surgical procedure (on an elective or urgent basis): infrainguinal arterial bypass, femoral endarterectomy, patch angioplasty will be included. Intervention: The intervention arm participants will be allocated to neuraxial anesthesia. The specific approach (spinal, epidural, or combined spinal and epidural) will be at the discretion of the treating anesthesiologist, as the underlying physiologic mechanisms and impacts are similar for both approaches. Outcomes and sample size: Primary outcome is monthly recruitment. Secondary outcomes are intervention adherence, retention, and elicitation of patient, clinician and researcher-identified barriers. Our pilot trial sample size estimate is informed by a power calculation for the future full-scale trial. In the future trial, a sample of 778 (389/arm) will provide 90% power using ANCOVA to detect the 5% minimally important between group difference in the continuous WHODAS score assuming a common standard deviation of 20 and a correlation with baseline of 0.4 (as observed in our previous work4) as well as accounting for up to 10% attrition and up to 10% cross-over. For the pilot trial, a sample size of 90 directly links to our 3 feasibility outcomes. Expertise: Our team features multidisciplinary clinical and methodological experts, nationally representative knowledge users and patient representatives. Expected outcomes: Our objective is for results of the planned full trial to change practice in caring for lower limb revascularization surgery patients.

Official Title
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Anesthesia for Lower Limb Revascularization to Optimize Functional ouTcomes

Conditions
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Surgery, Vascular Diseases, Peripheral Artery Disease

Intervention / Treatment
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* Procedure: neuraxial anesthesia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years Planned lower limb revascularization surgical procedure (on an elective or urgent basis): infrainguinal arterial bypass, femoral endarterectomy, patch angioplasty Able to access a telephone for postoperative follow-up Exclusion Criteria: Absolute contraindications to neuraxial anesthesia: impaired coagulation state (due to intrinsic, congenital or extrinsic (i.e., anticoagulant not held for guideline recommended period based on the American Society of Regional Anesthesia recommendations) factors), infection at the needle insertion point, increased intracranial pressure or intracranial mass, uncorrected hypovolemia or hypotension (systolic blood pressure <90 mmHg), severe uncorrected aortic stenosis) Traumatic arterial injuries as an indication for surgery Multiple sclerosis or demyelinating central nervous system conditions Known malignant hyperthermia or who require a malignant hyperthermia trigger-free anesthetic Pregnancy Prior enrollment in this study, or participating in another interventional trial that could interfere with interpretation of data for either study (may be acceptable if unrelated interventions/outcomes and study PIs mutually agree in writing to co-enrollment) Determination by the surgeon, anesthesiologist, or other clinician, that the patient would not be suitable for randomization

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Intervention arm participants will be allocated to neuraxial anesthesia. The specific approach (spinal, epidural, or combined spinal and epidural) will be at the discretion of the treating anesthesiologist, as the underlying physiologic mechanisms and impacts are similar for both approaches. Allowing clinician discretion will reflect routine standard of care practice and support generalizability. Specific choice of neuraxial anesthetic medications, doses, and adjuncts will also be at the discretion of the attending anesthesiologist, supporting pragmatism. While existing randomized data do not suggest that the sedation level during neuraxial anesthesia leads to differences in outcomes, providers will be requested to maintain sedation at or below a 3 on the Observer's Assessment of Alertness/Sedation scale (OAAS; mild to moderate sedation consistent to responding to verbal stimuli), the same approach used in a recent large pragmatic trial of anesthesia in hip fracture patients. | Procedure: neuraxial anesthesia<br>* Intervention arm participants will be allocated to neuraxial anesthesia.<br>|
| No Intervention: Control<br>Control group participants will be allocated to general anesthesia. Choice of anesthetic medications and doses will be at the discretion of each anesthesiologist as per routine standard of care, again supporting conduct of a pragmatic and generalizable trial. Similarly, choice of airway management strategies and anesthetic depth will also be based on patient and provider preference, as a recent large randomized trial demonstrates that anesthetic depth is not causally linked to risk of morbidity or mortality after surgery. Details of general anesthesia management and medications will be collected for all patients. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Monthly recruitment | Monthly recruitment of >=2 participants per center means that the full trial should be feasible | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intervention adherence | >=90% of participants were treated with allocated randomization arm to minimize the risk of contamination bias | 1 day | 
| Retention | >=90% of participants at the patient-reported primary outcome point of 30-days after surgery should minimize attrition bias in the definitive trial's primary outcome data | 30 days | 
| Elicitation of patient, clinician and researcher-identified barriers and facilitators | For study participants, at 30-day follow-up, a survey will be administered focusing on the acts of enrolling and being followed up in the trial. For research team members, a survey focused on the acts of participant recruitment and study support will be done once per site for all researchers, inclusive of clinician researchers and research staff, at approximately 3-4 months after study launch at their site. | 30 days, 120 days |