Correlation Between Acute Analgesia and Long-Term Function Following Ankle Injuries

NCT ID: NCT02667730

Last Updated: 2024-02-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 168 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-30
• Study Completion Date: 2021-12-31

Brief Summary

In this 4-arm pragmatic randomized control trial, the investigators hope to decipher whether the use of non-opioid analgesics (naproxen, celecoxib, acetaminophen) in addition to standardized physiotherapy during the acute phase of grade I-II ankle injuries will result in functional differences compared to standardized physiotherapy alone

Detailed Description

Background Ankle sprains occur frequently in the Canadian Armed Forces (CAF) population and account for a significant proportion of lost work time. Equally significant is the use of analgesics (NSAID or non-NSAID) (NSAID = non steroidal anti-inflammatory drug) in the CAF population. Existing literature suggests that the rate and extent of soft tissue healing may be adversely affected by use of some analgesics, particularly non-steroidal anti-inflammatory agents (NSAIDs), when these are used immediately following joint injury. There have been two postulated mechanisms for this observation: the first being that inflammatory markers are required in the regeneration process; the second is that the diminished pain level as a result of analgesic use encourages overuse of the injured tissue. Unfortunately, the science is far from conclusive, since much of it is derived based on isolated exercises, conducted in experimental settings, in older populations, or extrapolated from biomarkers that have not been validated for clinical relevance. While there is no current standard of practice regarding the use of pain relievers following ankle injury, this practice continues to be widespread in the CAF.

Goal The proposed study aims to clarify whether three commonly used non-opioid pain relievers provide additional benefit or delay improvement in ankle function following mild ankle sprains, when compared to standardized physiotherapy treatment alone. The three agents investigated will be 1) the non-steroid anti-inflammatory drug naproxen, 2) the selective anti-inflammatory celecoxib, and 3) the centrally-acting analgesic acetaminophen.

Methods Patients presenting to the health clinic at Garrison Petawawa with acute ankle injuries will be screened for study eligibility. All individuals who elect to participate in this study will be referred for standardized physiotherapy treatment, which will be administered according to study protocol. Participants will also be randomized to one of four analgesic treatment groups (i.e., naproxen, celecoxib, acetaminophen, or non-pharmacological measures only), with stratification for grade of ankle injury. Physiotherapists who are blinded to analgesic treatment allocation will evaluate participants' ankle function at 72 hours, 2 weeks, 3 months and 1 year post-injury, using previously validated tests. Pharmacists will assess response to drug therapy, side effects, and use of rescue medications at day 7 following enrollment. Occurrence of repeat ankle injuries and health resource consumption (i.e., specialist visits and diagnostic imaging) will also be assessed for the year following index injury.

Risks This study is intended to be low risk to participants as it is designed to closely mirror existing practices for such injuries. All medications used in this study are indicated for soft tissue injuries and their respective dosages/frequencies/durations aligned with manufacturer recommendations. The physiotherapy intervention was developed by Dr. Eric Robitaille. It has been used in previous studies and is currently in use in the CAF. The investigators do not expect the risk of injury to be higher than that associated with existing practices for ankle injuries.

Benefits Participants are expected to benefit from the direct application of a standardized physiotherapy treatment protocol for overall management of their condition as well as the pain relief from the analgesic options. The results of this study are expected to generate new information that can be readily applied to patient care, specifically in treating a frequently-occurring soft tissue injury in the CAF population.

Conditions

Ligament Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Physiotherapy only

This group will receive non-pharmacological advice and physiotherapy only

Group Type: PLACEBO_COMPARATOR

physiotherapy only

Intervention Type: OTHER

physiotherapy only (no drug)

Acetaminophen + physiotherapy

This group will receive acetaminophen 500mg 4 times daily for 7 days in addition to standardized physiotherapy

Group Type: EXPERIMENTAL

Acetaminophen

Intervention Type: DRUG

Acetaminophen 500 mg four times daily for 7 days

physiotherapy only

Intervention Type: OTHER

physiotherapy only (no drug)

Naproxen + physiotherapy

This group will receive naproxen 500mg twice daily for 7 days in addition to standardized physiotherapy

Group Type: EXPERIMENTAL

Naproxen

Intervention Type: DRUG

naproxen 500mg twice daily for 7 days

physiotherapy only

Intervention Type: OTHER

physiotherapy only (no drug)

Celecoxib + physiotherapy

This group will receive celecoxib 100mg twice daily for 7 days in addition to standardized physiotherapy

Group Type: EXPERIMENTAL

Celecoxib

Intervention Type: DRUG

celecoxib 100mg twice daily

physiotherapy only

Intervention Type: OTHER

physiotherapy only (no drug)

Interventions

Acetaminophen

Acetaminophen 500 mg four times daily for 7 days

Intervention Type: DRUG

Naproxen

naproxen 500mg twice daily for 7 days

Intervention Type: DRUG

Celecoxib

celecoxib 100mg twice daily

Intervention Type: DRUG

physiotherapy only

physiotherapy only (no drug)

Intervention Type: OTHER

Other Intervention Names

tylenol; celebrex

Eligibility Criteria

Inclusion Criteria

• Acquired acute ankle injury (injured less than 48 hours ago);
• Clinical diagnosis of a Grade I or II ankle sprain
• Is eligible to receive comprehensive medical care from Garrison Petawawa

Exclusion Criteria

• Diagnosis of ankle fracture or ligament rupture
• Has planned release from the Canadian Armed Forces within one year;
• Documented restrictions on military duties
• Has known intolerance or documented adverse reaction to acetaminophen or naproxen or celecoxib
• Documented history of liver or kidney problems
• pregnant or breastfeeding

• Minimum Eligible Age: 17 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Department of National Defense

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Koren Lui, BScPHM

Role: PRINCIPAL_INVESTIGATOR

Canadian Forces Health Services Group

Locations

2 Fd Amb medical clinic

Petawawa, Ontario, Canada

Countries

Canada

Other Identifiers

2013-12-126-004-0001

Identifier Type: -

Identifier Source: org_study_id