Etoricoxib in Acute Ankle Ligament Sprains

NCT00954785 | Withdrawn Phase 4 DMC

• 2 other identifiers: IISP 34251Rec Ref 005/2008
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Sprain

Keywords

ankle; ligament; sprain; non-steroidal anti-inflammatory drugs; treatment; Acute ankle ligament sprain

Outcome Measures

Primary Outcomes (1)

• Pain

  7 days

Secondary Outcomes (4)

• Swelling

  7 days

• Range of motion

  7 days

• Proprioception

  7 days

• Adverse events

  14 days

Study Arms (3)

Placebo drug

PLACEBO COMPARATOR

Device: Ankle brace

Etoricoxib

EXPERIMENTAL

Device: Ankle brace; Drug: Etoricoxib 120 mg mane

Diclofenac

ACTIVE COMPARATOR

Device: Ankle brace; Drug: Diclofenac 50 mg tds

Interventions

Ankle brace DEVICE

Sports Stirrup ankle brace (Aircast)

Diclofenac; Etoricoxib; Placebo drug

Diclofenac 50 mg tds DRUG

In the diclofenac group, each subject will receive 50 mg diclofenac in the morning, at mid-day and in the evening

Also known as: Voltaren

Diclofenac

Etoricoxib 120 mg mane DRUG

In the etoricoxib group, each subject will receive 120 mg etoricoxib in the morning, and placebo medication in the evening and at mid-day

Also known as: Arcoxia

Etoricoxib

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Cape Town: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

Kuilsriver Netcare Hospital, 33 Van Riebeeck Road, Kuilsriver

Cape Town, Western Cape, 7580, South Africa

Location

Sports Medicine Clinic, Sports Science Institute of South Africa

Cape Town, Western Cape, 7700, South Africa

Location

Related Publications (1)

• Jones P, Lamdin R, Dalziel SR. Oral non-steroidal anti-inflammatory drugs versus other oral analgesic agents for acute soft tissue injury. Cochrane Database Syst Rev. 2020 Aug 12;8(8):CD007789. doi: 10.1002/14651858.CD007789.pub3.

  PMID: 32797734 DERIVED

MeSH Terms

Conditions

Sprains and Strains

Interventions

Diclofenac; tyramine-deoxysorbitol; Etoricoxib

Condition Hierarchy (Ancestors)

Wounds and Injuries

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Sulfones; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Martin P Schwellnus, MBBCh, MD

  University of Cape Town

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 6, 2009
• First Posted: August 7, 2009
• Study Start: November 1, 2009
• Primary Completion: December 1, 2010
• Study Completion: July 1, 2011
• Last Updated: June 20, 2013

Record last verified: 2009-08

Locations

ZA (2)