Clinical trial NCT01731730: Study to Evaluate Safety/Efficacy of a Single Pre-Op Dose of AYX1 Injection to Treat Pain After Knee Replacement Surgery
Official title: Study to Evaluate the Safety & Efficacy of a Single Intrathecal Pre-Operative Administration of AYX1 Injection at Two Dose Levels Compared to Placebo in Patients Undergoing Unilateral Total Knee Arthroplasty (TKA)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Postsurgical Pain
Keywords: Postsurgical pain
Total knee arthroplasty
Total knee replacement
Lead sponsor: Adynxx, Inc.
Sponsor class: INDUSTRY
First posted: 2012-11-22
Enrollment: 102
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objectives of this proof of concept study are to evaluate the safety and preventive analgesic efficacy of a single preoperative intrathecal administration of AYX1 Injection in patients undergoing unilateral total knee arthroplasty.


Eligibility criteria: Inclusion Criteria:

* Scheduled to undergo primary unilateral TKA for painful osteoarthritis
* American Society of Anesthesiologists Physical Status Classification System ≤ 3
* Medically stable as determined by the Investigator based on pre-study medical history, physical/neurological examination, clinical lab tests, and 12-lead ECG findings
* Body mass index of 18-40 kg/m2
* Stable medical regimen for ≥ 1 month before randomization
* Able to read and understand study instructions in English, and willing and able to comply with all study procedures

Exclusion Criteria:

* More than 2 other current focal areas of pain, none greater in intensity than the target knee and no other active chronic pain conditions that would compromise operative knee pain evaluation
* Inflammatory arthridities (i.e., rheumatoid arthritis, lupus, ankylosing spondylitis, psoriatic arthritis, gout)
* Operative arthroscopy in the surgical knee in the last 6 months, or other prior surgery in either knee in the last 12 months, except for diagnostic arthroscopy
* Planned use of any of the following for TKA: general endotracheal anesthesia (GETA), peripheral nerve block (i.e., femoral nerve block), neuroaxial (intrathecal or epidural) opioids postoperatively, or knee capsule injections
* Received aspirin within 1 week of randomization, or any nonsteroidal anti-inflammatory drug (NSAID) within 5 half-lives prior to randomization, or planned use of NSAIDS post-operatively through Day 28
* Use of more than 20 mg per day (on average) of oral morphine or its equivalent within 1 month prior to randomization
* Use of adjuvant analgesics for chronic pain control (i.e., gabapentin, pregabalin) during the month prior to randomization or planned use post-operatively through Day 28
* Daily use of benzodiazepines in the 3 months prior to randomization (unless used for sleep and dosage will be consistent after surgery)
* Use of systemic corticosteroids (does not include inhaled steroids) within 3 months or intra-articular steroid injections within 1 month prior to randomization, or planned use of either post-op through Day 28
* Treatment with antibiotics or antivirals (EXCEPTION: topical treatments), immunosuppressives, antipsychotics, anticholinergics, or anticonvulsants within 1 month of randomization, with the exception of prescribed pre-surgical prophylactic antibiotics, and aspirin for cardiac prophylaxis (as long as discontinued within 1 week of randomization
* Current neurologic disorder, which could confound the assessment of pain (i.e., Parkinson's, Multiple Sclerosis)
* Current active depression symptoms
* Has had a change in dose or regimen of SSRIs or SNRIs for depression within 1 month of randomization
* Mini Mental State Exam score \< 24 at screening
* Current history of insulin dependent diabetes mellitus, or autoimmune conditions
* Severe chronic obstructive or restrictive pulmonary disease, current diagnosis of obstructive sleep apnea documented by a sleep laboratory study, or current home use of continuous positive airway pressure (CPAP) or bi-level positive airway pressure (BIPAP)
* Current evidence of alcohol abuse or history of alcohol-related complications within 1 year of randomization
* Known or suspected history of illicit drug abuse within 1 year before randomization, current or planned use of medical marijuana, or history of opioid dependence within 2 years before randomization
* Any malignancy within the past year, with the exception of basal cell carcinoma or uncomplicated or stable skin cancers documented to not require further or immediate treatment
* Women who are pregnant or nursing

Primary outcomes:
measure: Pain with walking during 5 meter walk test
timeFrame: 0-48 hours after surgery
measure: Pain with walking during 15 meter walk test
timeFrame: From hospital discharge to Day 28
Secondary outcomes:
measure: Total use of opioid medications (morphine equivalents) during hospital stay
timeFrame: 0-48 hours after surgery
measure: Total use of opioid medications (morphine equivalents) post-discharge to Day 28
timeFrame: From hospital discharge to Day 28
measure: Pain with 45 degrees of knee flexion
timeFrame: 0-48 hours after surgery
measure: Pain with 90 degrees of knee flexion
timeFrame: From 7 to 28 days after surgery
Other outcomes:
measure: Brief Pain Inventory functional interference scores at Days 7, 14, 21, 28, and 42
timeFrame: 7 to 42 days after surgery
Locations:
city: Sheffield
country: United States
state: Alabama
city: Phoenix
country: United States
state: Arizona
city: Boynton Beach
country: United States
state: Florida
city: Altoona
country: United States
state: Pennsylvania
city: Houston
country: United States
state: Texas
city: Nassau Bay
country: United States
state: Texas
city: Odessa
country: United States
state: Texas
Study officials:
affiliation: Adynxx, Inc.
name: Donald C Manning, MD, PhD
role: STUDY_DIRECTOR
References: