Clinical Trial Details
— Status: Recruiting
Administrative data
NCT number |
NCT04177433 |
Other study ID # |
Pro00092745 |
Secondary ID |
|
Status |
Recruiting |
Phase |
Phase 4
|
First received |
|
Last updated |
|
Start date |
December 2, 2020 |
Est. completion date |
December 31, 2024 |
Study information
Verified date |
May 2023 |
Source |
University of Alberta |
Contact |
Raelee Phillips, LPN |
Phone |
780-418-7410 |
Email |
raelee.phillips[@]albertahealthservices.ca |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
This randomized clinical trial (RCT) will evaluate 6-month outcomes following intra-articular
injections for arthritis of the thumb carpometacarpal (CMC) joint by comparing corticosteroid
plus local anesthetic versus saline (placebo) plus local anesthetic.
Description:
Background & Significance:
The burden of chronic diseases such as osteoarthritis (OA) is increasing globally, having a
major impact on both health services and society. 1,2 The CMC joint of the thumb is the most
commonly affected joint in the upper extremity by OA, and may lead to pain, decreased hand
function and poor health-related quality of life. 3-6 The prevalence of CMC OA varies
depending on the population being studied and is not yet well defined. Haara et al. 6
reported age-adjusted CMC OA prevalence of 7% in men and 15% in women among adults thirty
years of age or older in Finland. The ROTTERDAM study7 showed that 67% of the women and 54.8%
of the men had OA in at least one hand joint, with 35.8% occurring at the CMC joint. The
Framingham Study reported higher prevalence of symptomatic hand OA in women (26.2%) compared
to men (13.4%) aged 70 year or older. Symptomatic participants in this cohort had 10% reduced
maximal grip strength, reported more difficulty with activities of daily living such as
writing, handling, or fingering small objects (odds ratio = 3.4), and increased difficulty
lifting over 10-pound objects (odds ratio = 1.7 and 1.6, respectively).8
Treating CMC OA is challenging, since evidence is contradictory. A study looking at the
natural history of hand OA over a 6 year period showed variation in pain and functional
changes, with half of the population reporting deterioration of symptoms and the other half
reporting improvements of outcomes with different treatments. 9 Clinical changes (pain and
function) and radiographic progression of CMC OA were not related in this study. 9
Non-operative management (i.e. splints, medications, physiotherapy) is usually the first
choice of treatment for symptomatic CMC OA, followed by surgery if failed non-operative
management. 3,10 Current non-operative guidelines for treatment of hand OA are based on a
combination of research findings and expertise opinion. 11-13 2007EULAR, 2012 American
College of Rheumatology and 2014 NICE guidelines recommendations for the treatment of hand OA
include general considerations (i.e. clinical presentation, risk factors and associated
diseases), non-pharmacological (i.e. splint, education, exercises, thermal modalities), and
pharmacological (i.e. pain medications, oral and topical anti-inflammatories, opioids)
approaches. 11-13 2007EULAR and 2014 NICE also recommend intra-articular corticosteroid
injections as an adjunct treatment if patients didn't respond to other treatment approaches,
even though evidence is weak.11,13
Effectiveness of guided intra-articular injections for CMC OA evidence is inconsistent. There
is only one published RCT looking specifically at efficacy of corticosteroid injections in
CMC OA that found no clinical benefit from intra-articular corticosteroid injection to
moderate to severe CMC OA compared with placebo injection. This study ended earlier due to
recruitment issues and is underpowered to detect true differences between groups. 14 A
meta-analysis investigating intra-articular injections of corticosteroids or hyaluronic acid
in thumb OA stated that corticosteroids may be helpful in decreasing pain and hyaluronic acid
in improving pulp pinch force in a period of 5 to 6 months. 15 Due to high heterogeneity of
included studies in this meta-analysis, the evidence is still inconclusive. Another RCT
compared the efficacy of intra-articular hyaluronic acid and corticoid injections in CMC OA
and found that both study groups had decreased pain and improved function when compared to
baseline data, with no significant differences between groups. 16 A recent systematic review
on non-surgical therapies for hand OA found inconsistent evidence when comparing
intra-articular steroids and placebo. 17 They found three RCTs comparing intra-articular
steroids to placebo, with two studies showing no difference and one study showing significant
improvement in pain with movement between groups.17
Based on the lack of strong evidence regarding the use of guided corticosteroid injections to
treat CMC OA, this randomized clinical trial (RCT) will compare 6-months outcomes following
fluoroscopic guided injections of corticosteroid plus local anesthetic or saline (placebo)
plus local anesthetic in adult participants with carpometacarpal osteoarthritis (OA).
Our hypothesis is that participants undergoing guided intra-articular corticosteroid
injections will have better outcomes in the short -term, but not at the long term when
compared to the saline group.
Research Design & Methods:
Design: Randomized Control Trial Sample Size: Sample size was calculated based on repeated
measures ANOVA model with 2 groups and 4 time points (longitudinal approach), and group
effect (between subject effect) were examined for power analysis. Effect size (Cohen's f) was
considered from f=0.10 (small effect) to f=0.40 (large effect) increased by 0.05. Few
different correlations among repeated measures were considered (r=0.3 to 0.6 by 0.1). Based
on effect size f=0.25 (medium effect), approximately 62 to 90 participants will be required
as total sample size, with approximately 31to 45 participants per group.
Enrollment Procedures: Eligible participants presenting to primary care, rheumatologists or a
surgical consult will be introduced to the study. If the participant expresses interest, the
participant will complete the contact information form (assent to contact) and the Research
Coordinator will be notified. The Research Coordinator will contact the participant to
discuss the study in detail, obtain informed consent and book a baseline assessment.
Baseline Evaluation: Consented participants will undergo a baseline assessment with the
research coordinator who will be blinded to the treatment allocation. The assessment will
consist of 1) Quick-DASH, 2) Brief Michigan Hand Outcomes Questionnaire (Brief MHQ), 3) grip
and pinch strength using a handheld dynamometer, 4) socio-demographics (age, gender, height,
weight, handedness, smoking status, work/recreational sports information, duration of
symptoms, type of onset (insidious / traumatic) data). The participant will also complete the
Visual Analogue Scale (VAS) for pain intensity (rest and movement), and concomitant
treatments form (medications, splints, physiotherapy,…).
Randomization:
Participants will be randomized to one of the two groups once eligibility is confirmed and
participant is agreeable to be part of the study: Group A (intra-articular corticosteroid
injection + local anesthetic) or Group B (saline injection + local anesthetic). The
randomization sequence will be computer-generated in uneven blocks. Randomization codes will
be stored in opaque sequentially numbered envelopes and will be opened at baseline assessment
session. Participants and outcomes assessor will be blinded to the type of injection they
will be receiving.
Interventions:
- Fluoroscopic Guided Intra-articular Corticosteroid Injection plus local anesthetic:
Pre-filled opaque syringe containing 40 mg (1cc) of depo-medrol combined with 0.5 cc of
1% lidocaine (or 1cc saline + 0.5 cc 1% lidocaine) will be injected in the symptomatic
CMC joint using fluoroscopic imaging to ensure injection into the joint. If both CMC
joints are symptomatic, the most symptomatic joint will be injected. If both CMC joints
are equally symptomatic, the dominant hand will be injected. The surgeon and the
participant will be blinded to the injection content.
- Fluoroscopic Guided Intra-articular Saline Injection plus local anesthetic: Pre-filled
opaque syringe containing 0.5 cc of 1% lidocaine (or 1cc saline + 0.5 cc 1% lidocaine)
will be injected in the symptomatic CMC joint using ultrasound imaging to ensure
accuracy of injected location. If both CMC joints are symptomatic, the most symptomatic
joint will be injected. If both CMC joints are equally symptomatic, the dominant hand
will be injected. The surgeon and the participant will be blinded to the injection
content.
Follow-ups:
Follow-up research assessments will occur at:
• 6 weeks, 3- and 6-months: Assessment will be done by the research coordinator and will
include 1) Quick-DASH, 2) Brief MHQ, 3) Grip and Pinch strength, 4) Pain at rest and with
movement, 5) Concomitant treatments tracking.
The outcome assessor will be blinded to group allocation at all assessments points.
Outcomes/ Outcome Measures:
- Primary:
o Pain with movement at 3 months- Pain will be assessed using Visual Analogue Scale
(VAS) where zero equaled no pain and 10 the worst possible pain.18,19 VAS is a reliable
and valid method of measuring patient-reported pain and a minimal difference of 20 mm
(20%) among groups will be considered clinically important.20-22
- Secondary Outcomes:
- Quick Disabilities of the Arm, Shoulder and Hand (Quick-DASH) Questionnaire: it's a
11-item, patient-reported questionnaire that measures the function and psychosocial
impact of upper extremity musculoskeletal conditions in patients' quality of life.
It is scored between 0 (no disability) and 100(very disable).23 The Quick-DASH has
been widely used in clinical practice and research as a valid, reliable and
responsive tool to measure treatment outcomes from the patient's perspective after
upper limb injuries.24 The minimal important change expected is a 10-point
difference in mean DASH score among groups.24
- Brief Michigan Hand Outcomes Questionnaire (Brief MHQ): It is a 12-item
self-administered questionnaire that assess function, appearance, pain, and
satisfaction in patients with hand and wrist conditions and injuries, including
arthritis.
- Pinch Strength: Pinch strength will be measured with a mechanical pinch gauge that
is a reliable and valid method to detect difference in thumb strength.26 Pinch
strength will be measured using the following standard positions: 1) Tip pinch:
pinch between the thumb and index finger, and 2) Tripod pinch: pinch between the
thumb, index and middle fingers.26 A minimal difference of 0.33 kg for tip and 0.35
kg for tripod pinch among groups will be considered clinically important.26
Statistical Analysis: Statistical analysis will use Intention-to-Treat approach with all
outcomes attributed to the assigned group. Descriptive statistics will be used for group
comparisons with independent t-tests for continuous and Pearson Chi-square or Fisher's Exact
tests for categorical variable at baseline and for possible complications/adverse events.
Linear Mixed Modeling (LMM), adjusted for gender and employment, will compare pain,
Quick-Dash, Brief MHQ and pinch strength between groups over the 6-months evaluation period.
The level of significance will be set at α=0.05. Statistical analysis will use the following
software: SPSS version 25.0, SAS version 9.4, and R version 3.5.2.