Clinical trial NCT04818749: Combined Intravenous Dexamethasone and Dexmedetomidine as Adjuncts to Popliteal and Saphenous Nerve Blocks in Patients Undergoing Orthopaedic Surgery of the Foot and Ankle
Official title: Combined Intravenous Dexamethasone and Dexmedetomidine as Adjuncts to Popliteal and Saphenous Nerve Blocks in Patients Undergoing Orthopaedic Surgery of the Foot and Ankle. A Randomised, Blinded, Placebo-controlled, Parallel Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Anesthesia, Local
Keywords: Regional anesthesia
Dexamethasone
Dexmedetomidine
Adductor canal block
Saphenous nerve block
Popliteal nerve block
Peripheral nerve block
Lead sponsor: Zealand University Hospital
Sponsor class: OTHER
First posted: 2021-03-26
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomised, blinded, placebo-controlled, parallel clinical trial
Primary purpose: TREATMENT

Brief summary: The investigators will investigate the beneficial and harmful effects of combining dexamethasone (12 mg) and dexmedetomidine (1mcg/kg) as adjuncts to popliteal and saphenous nerve blocks in patients undergoing surgery of their foot or ankle.

Detailed description: This is a randomised, blinded, placebo-controlled, multicentre, parallel, 3-arm clinical trial assessing the effects of adjunct intravenous dexamethasone + dexmedetomidine 1mcg/kg versus intravenous dexamethasone 12mg versus intravenous placebo on time to first pain (i.e. block duration) in patients undergoing surgery of the foot or ankle. All participants will receive a sciatic and saphenous nerve block and general anesthesia.

The investigators will randomise participants to either intervention arm. Participants will be allocated according to a computer-generated random allocation sequence with random permuted blocks and stratification by site. The allocation will be concealed in sequentially numbered opaque envelopes that will not be opened before the participant has been allocated to that specific allocation number/envelope. Trained trial personnel not otherwise involved in the trial will prepare the trial medication according to the allocation.

All others involved will be blinded for the entire duration of the trial (participant, carers, investigators, people delivering the intervention, observers/outcome assessors, statisticians). Blinding will not be broken until agreement has been reached within the steering committee regarding the statistical analysis. The trial medication is prepared in identical syringes with 20ml of identically appearing trial medication. The syringes are subsequently marked with 'syringe 1' and 'syringe 2' and delivered to the investigators. Syringe 1 either contains 12mg dexamethasone or saline and will be administered prior to block performance using an infusion pump set to deliver the volume over 12 minutes. Syringe 2 either contains 1 mcg/kg dexmedetomidine or saline and will be administered after block performance and general anesthesia over 30 minutes using an infusion pump, thereby masking the sedative effect of the dexmedetomidine. The investigators will not be present in the operation room during surgery.

The investigators expect little to no attrition bias since the intervention is simple with a short follow-up. The investigators expect some missing data for duration of the motor block, as most participants will have the affected limb immobilized post-surgery, thereby making assessment of return of motor function difficult.

The statistical analysis plan was pre-defined prior to unblinded data becoming available and can be found on: https://doi.org/10.6084/m9.figshare.22491214.

Eligibility criteria: Inclusion Criteria:

* Scheduled for unilateral osseous surgery of the ankle or foot
* General anaesthesia with both a popliteal and a saphenous nerve block for postoperative analgesia
* Age of 18 or above
* American Society of Anaesthesiologists Physical Status Score of 1 to 3
* Body Mass Index of 18 to 40, but a minimum weight of 50 kg.
* For fertile women, negative urine humane choriongonadotropine test and use of safe anti-conception
* Ability to understand the trial protocol, risks, benefits, and provide signed informed consent

Exclusion Criteria:

* Inability to read and understand Danish
* Uncooperativeness (as judged by investigators)
* Participation in another trial involving medication
* Allergy to study medication
* Daily use of opioids above 30 mg/day morphine (or equivalents)
* Daily use of corticosteroids of more than 5 mg prednisolone equivalents within the past one month
* Neurological or musculoskeletal disease making block performance impossible (as judged by investigators)
* Dysregulated diabetes (as judged by investigators)
* Dysregulated anticoagulants (as judged by investigators)
* History of drug or alcohol abuse
* Glaucoma
* Contraindications for paracetamol or opioids
* Contraindications to general anaesthesia
* Other concomitant conditions needing surgery
* Other concomitant traumatic injuries

Primary outcomes:
measure: Time to first pain (measured in minutes)
timeFrame: 72 hours
Secondary outcomes:
measure: Duration of the motor block (measured in minutes)
timeFrame: 72 hours
measure: Quality of sleep (measured on the Numerical Rating Scale) postoperative night 1
timeFrame: 24 hours
measure: Quality of sleep (measured on the Numerical Rating Scale) postoperative night 2
timeFrame: 48 hours
measure: Quality of sleep (measured on the Numerical Rating Scale) postoperative night 3
timeFrame: 72 hours
measure: Proportion of participants with one or more serious adverse events
timeFrame: 30 days
measure: Proportion of participants with one or more adverse events not considered to be serious
timeFrame: 72 hours
Other outcomes:
measure: Cumulative oxycodone consumption (measured in milligrams) at 24 hours
timeFrame: 24 hours
measure: Cumulative oxycodone consumption (measured in milligrams) at 48 hours
timeFrame: 48 hours
measure: Cumulative oxycodone consumption (measured in milligrams) at 72 hours
timeFrame: 72 hours
measure: Pain (measured on the Numerical Rating Scale) at 24 hours postoperatively
timeFrame: 24 hours
measure: Average pain (measured on the Numerical Rating Scale) from 0 to 24 hours postoperatively
timeFrame: 24 hours
measure: Worst pain (measured on the Numerical Rating Scale) from 0 to 24 hours postoperatively
timeFrame: 24 hours
measure: Pain (measured on the Numerical Rating Scale) at 48 hours postoperatively
timeFrame: 48 hours
measure: Average pain (measured on the Numerical Rating Scale) from 24 to 48 hours postoperatively
timeFrame: 48 hours
measure: Worst pain (measured on the Numerical Rating Scale) from 24 to 48 hours postoperatively
timeFrame: 48 hours
measure: Pain (measured on the Numerical Rating Scale) at 72 hours postoperatively
timeFrame: 72 hours
measure: Average pain (measured on the Numerical Rating Scale) from 48 to 72 hours postoperatively
timeFrame: 72 hours
measure: Worst pain (measured on the Numerical Rating Scale) from 48 to 72 hours postoperatively
timeFrame: 72 hours
measure: Patient satisfaction (added after initiation of the trial, will only be available for a subset of the patients)
timeFrame: 72 hours
Locations:
city: Køge
country: Denmark
facility: Department of Anaesthesiology
state: Zealand Region Of Denmark
city: Copenhagen
country: Denmark
facility: Department of Anaesthesiology, Bispebjerg Hospital
Study officials:
affiliation: Department of Anaesthesiology, Zealand University Hospital, Køge, Denmark
name: Mathias Maagaard, MD
role: PRINCIPAL_INVESTIGATOR
References: