Etoricoxib in Acute Ankle Ligament Sprains

This study has been withdrawn prior to enrollment.
(The study was terminated by Merck USA. The company did not supply drugs for the study.)
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by:
University of Cape Town
ClinicalTrials.gov Identifier:
NCT00954785
First received: August 6, 2009
Last updated: June 19, 2013
Last verified: August 2009
  Purpose

The aim of the study is to measure the effectiveness of treatment over 7 days with commonly used anti-inflammatory medications namely etoricoxib and diclofenac (Voltaren) on reducing the severity of pain, swelling and loss of function (range of movement, proprioception) arising from a mild to moderate sprain (partial tear) of the lateral (outer) ligaments of the ankle joint. This injury is commonly known as an ankle sprain.


Condition Intervention Phase
Sprain
Device: Ankle brace
Drug: Diclofenac 50 mg tds
Drug: Etoricoxib 120 mg mane
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: The Efficacy and Safety of Administration of the COX-2 Selective NSAID, Etoricoxib (120mg od. for 7 Days) Compared to Diclofenac (50 mg Tds. for 7 Days) and Placebo as Adjunct Treatment in the First 7 Days of Treatment of Acute Grade II Lateral Ankle Ligaments Sprains: A Clinical Trial

Resource links provided by NLM:


Further study details as provided by University of Cape Town:

Primary Outcome Measures:
  • Pain [ Time Frame: 7 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Swelling [ Time Frame: 7 days ] [ Designated as safety issue: No ]
  • Range of motion [ Time Frame: 7 days ] [ Designated as safety issue: No ]
  • Proprioception [ Time Frame: 7 days ] [ Designated as safety issue: No ]
  • Adverse events [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]

Enrollment: 0
Study Start Date: November 2009
Estimated Study Completion Date: July 2011
Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo drug Device: Ankle brace
Sports Stirrup ankle brace (Aircast)
Experimental: Etoricoxib Device: Ankle brace
Sports Stirrup ankle brace (Aircast)
Drug: Etoricoxib 120 mg mane
In the etoricoxib group, each subject will receive 120 mg etoricoxib in the morning, and placebo medication in the evening and at mid-day
Other Name: Arcoxia
Active Comparator: Diclofenac Device: Ankle brace
Sports Stirrup ankle brace (Aircast)
Drug: Diclofenac 50 mg tds
In the diclofenac group, each subject will receive 50 mg diclofenac in the morning, at mid-day and in the evening
Other Name: Voltaren

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age 18 to 45 years (Rationale: Most injuries occur in this age group, older subjects are more likely to have concomitant pathology e.g. osteoarthrosis)
  • Acute lateral ankle ligament sprain less than 48 hours ago (Rationale: It is important to standardize the phase of the injury and enter at the time of the maximum inflammatory response, but this has to be balanced with enough time to allow injured subjects to access the treatment facility, and that all measurements can be completed)
  • Grade II ankle sprain injury according to the following: (Rationale: Standard clinical criteria are used to ensure that the severity of injury is similar in all subjects)

    • Mild to moderate pain (> 40mm on the VAS)
    • Mild to moderate lateral ankle swelling (Greater than 5% increase in ankle volume compared with the uninjured side according to volumetric assessment)
    • Tenderness over the anterior talofibular ligament
  • Negative urine and serum pregnancy test (females only) with signed undertaking on use of adequate contraception for the duration of the trial (Rationale: This is to make sure that no pregnant female subjects are entered or can become pregnant during the trial as a safety precaution against drug use in pregnancy)
  • No use of analgesics or oral or intramuscular anti-inflammatory drugs in the last 24 hours (Rationale: This is to ensure that at the time of the first assessment, no subject has taken oral or intramuscular medication that may influence the initial assessments of pain and swelling)
  • No use of topical anti-inflammatory agents, ice application or compression in the last 12 hours (Rationale: This is to ensure that at the time of the first assessment, no subject has taken topical medication, or used ice or compression that may influence the initial assessments of pain and swelling)

Exclusion Criteria:

  • Patients with a history of an ankle sprain in the previous 12 months (Rationale: A recent previous injury in the ligaments may affect the healing of a new injury)
  • The presence of an ankle fracture as diagnosed on normal radiographs - using the Ottowa ankle rules. (Rationale: This is to ensure that subjects only suffer from a soft tissue injury, so that the study group is homogeneous)
  • Patients who have experienced bronchospasm, acute rhinitis, nasal polyps, angioneurotic oedema, urticaria, or allergic-type reactions after taking acetylsalicylic acid, NSAID's,(including COXIBS) , antipyretics or any of their excipients. (Rationale: This is to ensure that no subject who has a history of hypersensitivity to drugs is given drugs that may cause an allergic reaction)
  • Patients who have a sulphonamide allergy. (Rationale: This is to ensure that no subject who has a history of hypersensitivity to certain drugs is given drugs that may cause an allergic reaction)
  • Active peptic ulcer within the previous six months (Rationale: It is well established that NSAID's have gastric irritation, gastritis, and ulceration with haemorrhage as possible side effects. This is to ensure that subjects with a history of these syndromes are not included as a safety issue)
  • History of recurrent peptic (gastric or duodenal) ulcer (Rationale: It is well established that NSAID's have gastric irritation, gastritis, and ulceration with haemorrhage as possible side effects. This is to ensure that subjects with a history of these syndromes are not included as a safety issue)
  • History of any bleeding disorders, including gastrointestinal bleeding or cerebrovascular bleeding (Rationale: It is well established that non-selective NSAID's can decrease clotting. This is to ensure that subjects with a history of these syndromes are not included as a safety issue)
  • Patients with severe congestive heart failure (NYHA 3 - 4) (Rationale: The administration of etoricoxib is contra-indicated in these patients)
  • Patients with a medical history of ischemic heart disease or cerebrovascular disease. (Rationale: There is a potential risk of cardiovascular events with COX-2 selective inhibitor use, although this is only documented after long-term use (>18 months).
  • History of cardiac failure, left ventricular dysfunction, hypertension or pre-existing oedema. (Rationale: Inhibition of prostaglandin synthesis, as caused by these drugs, may cause fluid retention, oedema and hypertension.
  • Patients with peripheral arterial disease (Rationale: Peripheral aerial disease will alter the response to healing in the ankle ligaments)
  • Patients with a history or current symptoms and clinical signs of severe impairment of renal function (CrCl <30 ml/min) or moderate to severe impairment of hepatic or function (Rationale: The administration of etoricoxib 120 mg is contra-indicated in these patients)
  • Patients with inflammatory bowel disease. (Rationale: The administration of etoricoxib is contra-indicated in these patients).
  • Patients consuming more than three alcoholic drinks per day, or patients with a history of alcohol abuse (Rationale: Excessive alcohol intake could negatively affect liver function, interfere with drug metabolism and reduce compliance to the protocol)
  • Patients with hereditary problems of galactose intolerance, Lapp lactose deficiency or glucose-galactose malabsorption. (Rationale; etoricoxib tablets contain lactose and is therefore contraindicated in these patients)
  • Currently pregnant or lactating (Rationale: The administration of etoricoxib is contra-indicated in these patients)
  • Woman attempting to conceive. (Rationale: Any drug known to inhibit COX-2 is contra-indicated)
  • Concomitant treatment with anti-coagulants (including heparin, warfarin, and ticlopidine) (Rationale: It is well established that NSAID's can decrease clotting. This is to ensure that subjects with a history of established bleeding disorders or those on anti-clotting therapy are not included as a safety issue).
  • Concomitant treatment with lithium, methotrexate, angiotensin converting enzyme inhibitors, beta-blockers and diuretics) (Rationale: NSAID's have significant drug interactions with some medications, can potentiate or impair the effects of others and therefore patients on these medications are excluded for safety reasons).
  • Concomitant administration of other NSAID's (including aspirin doses > 150 mg) or analgesic agents (Rationale: The purpose of the study is to determine the effects of specific NSAID's on pain and swelling. Concomitant use of other NSAID's will interfere with outcome measures and these patients have to be excluded from the study)
  • Concomitant administration of cyclosporine and tacrolimus. (Rationale: Co-administration of these medications with any NSAID's may increase their nephrotoxic effects)
  • Concomitant treatment of etoricoxib with rifampicin. (Rationale: Rifampicin is a potent inducer of CYP enzymes and produces a 65% decrease in etoricoxib plasma concentration.)
  • Current treatment or treatment within the last two months with corticosteroids (systemic, intra-articular) (Rationale: Long acting corticosteroids can interfere with outcome measures and patients who received these medications have to be excluded from the study)
  • Participation in another clinical trial during this study or during the previous month (Rationale: This is to ensure that patients who may still have effects from treatment administered during another trial are not included)
  • Inability to comply with the protocol (Rationale: This is to exclude subjects who will not be able to complete the study)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00954785

Locations
South Africa
Sports Medicine Clinic, Sports Science Institute of South Africa
Cape Town, Western Cape, South Africa, 7700
Kuilsriver Netcare Hospital, 33 Van Riebeeck Road, Kuilsriver
Cape Town, Western Cape, South Africa, 7580
Sponsors and Collaborators
University of Cape Town
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Martin P Schwellnus, MBBCh, MD University of Cape Town
  More Information

No publications provided

Responsible Party: Martin Schwellnus, Prof, University of Cape Town
ClinicalTrials.gov Identifier: NCT00954785     History of Changes
Other Study ID Numbers: IISP 34251, Rec Ref 005/2008
Study First Received: August 6, 2009
Last Updated: June 19, 2013
Health Authority: South Africa: Medicines Control Council
United States: Food and Drug Administration

Keywords provided by University of Cape Town:
ankle
ligament
sprain
non-steroidal anti-inflammatory drugs
treatment
Acute ankle ligament sprain

Additional relevant MeSH terms:
Diclofenac
Etoricoxib
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Central Nervous System Agents
Cyclooxygenase 2 Inhibitors

ClinicalTrials.gov processed this record on October 16, 2014