Chlorzoxazone in Hip and Knee Arthroplasty
Information source: Northern Orthopaedic Division, Denmark
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Osteoarthritis of Hip; Osteoarthritis, Knee
Intervention: chlorzoxazone (Drug); Placebo (Drug); THA (Procedure); TKA (Procedure)
Phase: Phase 4
Status: Not yet recruiting
Sponsored by: Northern Orthopaedic Division, Denmark Official(s) and/or principal investigator(s): Michael U Jensen, DMSc,PhD,MD, Principal Investigator, Affiliation: Northern Orthopaedic Division, Denmark Mogens B Laursen, MD, PhD, Study Chair, Affiliation: Northern Orthopaedic Division, Denmark
Overall contact: Michael U Jensen, DMSc,PhD,MD, Phone: +4551882306, Email: michael@hoftekirurgi.dk
Summary
The purpose of this study is to elucidate whether patients operated with THA and TKA can
benefit from treatment with chlorzoxazone.
Clinical Details
Official title: Analgetic Effects of Chlorzoxazone in Total Hip and Knee Arthroplasty
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Pain after 5 meter walk
Secondary outcome: Oxford Hip/Knee scorePain at rest worst pain for the last 24 hours
Detailed description:
Introduction and rationale Background Modern treatment of pain following surgery based on
multimodal analgesic strategy where the pain system different points of attack struck with
different types analgesics. This also tries to reduce the consumption of opioids associated
with frequent side effects like nausea, vomiting, constipation, difficulty urinating,
weather stretch problems and Lethargy.
But in spite of intense research over the last decades, is pain after arthroplastic surgery
in hip (total hip arthroplasty (THA)) or knee (total knee replacement (TKA)) continue a
significant clinical problem. It is a current clinical assumption that patients with pain in
the hip or knee region immediately after TKA or THA have tense muscles, which reinforces
pain behavior. The mechanism for such muscle tension is not fully understood.
For many years the investigators have been on Danish orthopedic departments dealt with these
patients with postoperative pain after major joint prosthesis operations with the muscle
relaxant chlorzoxazone. On some sections included in the standard chlorzoxazone
prescriptions for pain after hip and knee replacement.
chlorzoxazone has for many years been marketed for the treatment of pain in skeletal muscle
by inhibition of mono- and polysynaptic reflexes in the CNS. The muscle relaxing effect is
mediated by inhibitory effects on spinal polysynaptic reflexes. In placebo-designed clinical
studies of chlorzoxazone's beneficial effect on heterogeneous groups of patients with
spasticity, motor neuron syndromes, as well as muscle pain and spasm of peripheral
musculoskeletal diseases have not been able to demonstrate no significant analgesic effect;
chlorzoxazone have also failed to show pain-relieving effect in the treatment of back pain
It is remarkable that in spite of the widespread use of chlorzoxazone not can be found only
one study of chlorzoxazone used as adjuvant pain relieving treatment after hip or knee
surgery (or other orthopaedic treatment). The current clinical practice is therefore made on
purely empirical basis. The effect must be considered as uncertain, but may in some cases be
indicated, most often as an adjunct to other therapy, for example analgesics,
anti-inflammatory agents, physiotherapy or even training. In such cases, regarded
chlorzoxazone be an alternative to benzodiazepines. There is therefore a need for a
prospective, randomized, double-blind, placebo-controlled study evaluating the potential
analgesic effect of chlorzoxazone. In this intervention study is the selected dosage of
chlorzoxazone set at based on the recommendation of the Danish Medicines Information A / S 7
(http://pro. medicin. dk/Medicine / Preparations / 638) and Takeda Pharma A / S. The latter
produces chlorzoxazone. The recommendation is based on our current knowledge of
chlorzoxazones pharmacodynamic and pharmacokinetic properties. chlorzoxazone given in this
study as tablet chlorzoxazone, 250 mg, 3 times daily for the first seven postoperative days.
Adverse reactions to chlorzoxazone are well known. They are relatively few, mostly mild and
transient. The most frequent adverse events related to chlorzoxazone, fatigue and dizziness
(about 1-10% of patients) Adverse reactions are to some extent overlapping with the side
effects that are related to the perioperative opioid treatment. It is therefore possible
that the frequency of adverse events overall is reduced if chlorzoxazone found to be
analgesic (and opioid-sparing). Patients will be hospitalized for a minimum of two nights
after surgery and thus be close observation in the period in which the risk of side effects
is greatest. At the same time, all patients undergo standardized adverse event registration.
If, contrary to expectations unexpected or unacceptable side effects medication will
promptly be interrupted. The study involves a group of patients (THA and TKA), which is an
important clinical pain problem. All of these patients receive a well-implemented and
evidence-based treatment. Thus, anesthesia, analgesia and surgical procedure standardized
for all patients receiving concomitant consequences usual principles of early mobilization
8; 9th The planned randomized, double-blind, placebo-controlled design in which all patients
receive the same and standardized interventions, enabling the best possible evaluation of
modality under study intervention with chlorzoxazone vs. placebo). The level of pain after
surgery as the primary endpoint, recorded by means of a well-tested and validated tool
(visual analog scale (VAS)) 48 hours after operation. The current study could contribute to
a clarification of the postoperative analgesic effect of chlorzoxazone immediately after THA
and TKA. As secondary endpoints, the patients functional level be determined Oxford Hip /
Knee Score 7 days after surgery. Furthermore, a number of tertiary parameters related to
pain, function and side effect profile be determined as shown in Table 1. Evidence in this
area will be of immediate benefit to patients operated with THA and TKA - and maybe for
other surgical patients.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Planned primary unilateral THA or TKA
- Patients (male/female) ≥ 18 år
- Patients giving written informed consent and authority.
- Patients receiving spinal anaesthesia
Exclusion Criteria:
- Patients with intolerance to trial medications
- Rejection of or contraindicated spinal anaesthesia
- Patients with rheumatoid arthritis.
- Patients with Body Mass Index (BMI) ≥ 35
- Patients that do not read or write Danish
Locations and Contacts
Michael U Jensen, DMSc,PhD,MD, Phone: +4551882306, Email: michael@hoftekirurgi.dk
Northern Orthopaedic Division, Clinik Farsoe, Aalborg University Hospital, Farsoe, Northern Jutland, Denmark; Recruiting Mogens B Laursen, MD, PhD, Phone: +4520946846, Email: mogens.berg.laursen@rn.dk
Additional Information
Starting date: September 2015
Last updated: August 4, 2015
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