Overview
The TOP-MAP pilot trial has multiple goals. The first goal of this pilot clinical trial is to find out if it will be possible to carry out a study at multiple pediatric emergency department sites (Peds ED) comparing Non-Steroidal Anti-Inflammatory (NSAID) gel applied to a new ankle or knee injury to NSAIDs taken by mouth in kids aged 6-18. The investigators want to determine if the gel works as well or better at reducing pain than NSAIDs given by mouth. Based on studies done on adults, the investigators know that NSAIDs that are applied directly to an injury work as well at relieving pain as NSAIDs that are taken by mouth. Another goal of this pilot trial is to determine if it is possible to recruit participants to the study, and if the participants complete the questionnaire and take the medications as prescribed on Day 1.
The participants will be in the study for 14 days. Participants will be required to take the oral NSAID medication and to apply the topical NSAID gel 3 times a day for the first 3 days after their visit to the ED. The investigators will ask the participants to rate their pain on a scale of 0 (no pain) to 10 (worst pain ever) before and after they use the medicine. On day 7, the participants will rate their pain, and their activity level. On day 14 participants will do the same.
Description
In Canada, musculoskeletal sprains and strains account for 10% of Emergency department visits in children aged 10-17 years of age. Unlike upper limb injuries, which are often fractured, injuries to the ankle and knees are non-fractured soft tissue injuries in 88% and 91% respectively. Management of such injuries is focused on pain and inflammation management through pharmacotherapy, cryotherapy and early mobilization while avoiding casting.
Oral ibuprofen, a non-steroidal anti-inflammatory drug (NSAID) is the recommended first-line pharmacotherapy for mild to moderate musculoskeletal (MSK) injury related pain. However, alternatives such as topical NSAIDs (e.g., diclofenac emulgel) are commonly recommended in adults. Among adults their effect is equivalent to oral NSAIDs and they can be directly applied to the injured area resulting in a lower risk of systemic adverse events (AE's). Despite their frequent use in adults, topical NSAIDs are currently not recommended for children due to a lack of supporting data.
Based on adult data, the investigators hypothesize that topical NSAIDs provide similarly effective pain management to oral NSAIDs in children with acute MSK injuries with a reduced risk of systemic AEs. This pilot trial will assess the feasibility of a definitive non-inferiority trial of topical diclofenac emulgel vs. oral ibuprofen for children with acute ankle or knee soft tissue injuries. The results of a definitive trial have the potential to alter current pediatric MSK injury management if topical diclofenac emulgel is indeed non-inferior to oral ibuprofen for pain relief, with an expected lower risk of systemic AEs.
In children aged 6 to \<18 years with an acute (≤4-days) ankle or knee non-fractured soft tissue injury (e.g., sprain, strain or contusion), is topical diclofenac emulgel 11.6 mg/g non-inferior to oral ibuprofen (both administered three times daily) in reducing pain during the 72 hours following ED discharge? This pilot randomized, double-dummy, blinded (participants, clinicians, outcome assessors, investigators), two-centre ED trial will enroll 60 participants, following the 2010 CONSORT statement.
Study medications will be administered simultaneously to maintain masking of participants and accuracy of pain assessments, three times daily for the first 72 hours, followed by as-needed dosing for a total of 14 days.
This pilot will inform the planning of a definitive trial by assessing a) feasibility of recruiting patients in EDs; b) acceptability of interventions; c) ability to collect at-home pain assessments; d) identifying pain assessment time-point with the highest completion and effect; and e) refining sample size calculations from variance around clinical outcomes data. The investigators will evaluate the impact of the eligibility criteria and identify which groups of children are being excluded and why. This data will be used to inform discussions to finalize the eligibility criteria.
Eligibility
Inclusion Criteria:
- Age 6 to 18 years old.
- Injury less than or equal to 4 days old
- Non-fractured MSK soft-tissue injury (ankle or knee, confirmed clinically and/or radiographically)
- Pain score of more than or equal to 3 on the verbal numerical rating scale, with movement in the past 2 hours or before analgesia
- Willing and able to complete follow-up surveys as per study protocol
Exclusion Criteria:
- Previous enrolment in the trial
- Barriers to topical treatment application, including skin conditions (e.g. eczema, infection, open wounds) or overlying material (e.g., rigid cast) which would make applying topical treatment impossible.
- Any other history, condition, therapy, or uncontrolled intercurrent illness, which could, in the opinion of the Qualified Medical Investigator or treating physician, would make the participant unsuitable for this study
- Any contraindication to NSAID use including but not limited to a history of GI bleeding, gastric ulcer, inflammatory bowel disease, prior cerebrovascular bleeding, bleeding diathesis, interstitial kidney disease
- Taking NSAIDs daily for other indications (e.g, chronic pain or arthritis)
- Known hypersensitivity to ibuprofen, diclofenac or other NSAIDs.
- Any known allergy or intolerance to any components or trace constituents (e.g., aloe vera, tree nuts or corn) of the investigational products
- Current use of prohibited medications known to impair renal function when combined with NSAIDs or cause potential additive risks of gastrointestinal toxicity and renal impairment
- Absence of a parent/guardian for children who are not mature minors.
- Caregiver and/or child cognitive impairment precluding the ability to complete study procedures
- Inability to obtain consent, and to complete follow-up surveys due to language barrier
- Known or suspected late pregnancy (gestational age ≥20 weeks) at the time of enrolment or breastfeeding females, due to the risk of premature closure of the ductus arteriosus associated with NSAID use
- Current enrollment in another pain-related clinical trial or in a study that, in the opinion of the Qualified Medical Investigator, may interfere with enrollment, involve investigational products that interact with study medications, or compromise follow-up and outcome assessment
