Primary objective: to assess whether an intra-muscular gluteal corticosteroid injection is non-inferior to an intra-articular knee corticosteroid injection on knee pain in patients with knee osteoarthritis in general practice at 4 weeks follow-up.…
ID
Source
Brief title
Condition
- Joint disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome is patient reported severity of pain measured with the KOOS
pain scale 4 weeks after the injection.
Secondary outcome
1)Patients* reported adverse events will be assessed with a questionnaire 2
weeks after injection. Patients will be asked to report hospitalization in the
questionnaires at 4, 8, 12 and 24 weeks as a proxy for SAEs.
2)Knee pain (KOOS) at all time points (baseline, 2, 8, 12, 24 weeks);
3)Knee pain severity averaged over last week will be measured with an 11-point
numerical rating scale (NRS:0-10; 0=no pain);
4)Severity of global osteoarthritis pain will be measured with the WOMAC pain
and will be calculated from the KOOS questionnaire (0-100; 0=extreme pain);
5)Intermittent and constant osteoarthritis pain will be measured with the ICOAP
(0-100: 0=no pain);
6)Knee complaint characteristics (duration of symptoms at baseline, sensation
of swelling in the knee as an indicator of flare-up)
7)Disability will be measured with the KOOS Function in daily living (0-100;
0=extreme problems).
8)Health related QoL will be measured with the EQ-5D-5L (scores ranging from
-0.446=worst health related QoL to 1.0=perfect health related QoL);
9)Patients* perceived recovery measured with a 7-point Likert scale that will
be dichotomized in recovered (score 1 *complete recovery* and 2 *much improved)
and not-recovered (score 3 *improvement* to score 7 *worse than ever*);
10)Percentage responders is defined by the OMERACT-OARSI criteria: High
improvement (*50%) in KOOS pain subscale or in KOOS function in daily living
subscale and absolute increase *20 points in KOOS pain subscale or function in
daily living subscale, if not then improvement in at least 2 of the 3 following
domains: 1) *20% improvement in KOOS pain subscale and *10 points increase in
KOOS pain subscale, 2) *20% improvement in KOOS function in daily living
subscale and *10 points increase in KOOS function in daily living subscale, 3)
*20% increase in global score and *10 points increase in global score. In this
study patients* global assessment will be measured with a patients* perceived
recovery score measured on a 7-point Likert scale. This domain is considered
improved if a patient fills in score 1 *complete recovery*, score 2 *much
improved*, or score 3 *slightly improved*;
11)Co-interventions including medication, non-drug therapies such as
physiotherapy, referrals and surgery will be measured with the modified iMCQ;
12)Experienced painfulness of injection.
Background summary
The knee is the most affected joint in osteoarthritis and mainly managed by GPs
in the Netherlands. The prevalence of knee osteoarthritis in general practice
is estimated at 33.7 per 1000 registered patients (24.2 men; 43.1 women).
The recent updated version (2016) of the NHG guideline *Non-traumatic knee
complaints* recommends to start with advice and/or counseling regarding the
course of knee osteoarthritis, in combination with advice on the importance of
regular physical activity and reducing body weight if applicable4. If there is
an unsatisfactory effect of these first measures a referral for exercise
therapy under the supervision of a physiotherapist may be considered.
Analgesics (paracetamol, NSAID) can be prescribed for knee pain. When there is
an interim aggravation or insufficient pain relief an intra-articular
corticosteroid injection with 20 to 40 mg triamcinolone acetonide is commended.
Intra-articular corticosteroids appear to cause as many adverse events as a
placebo. However, there is no precise and reliable information about the
adverse events of intra-articular corticosteroids available. Intra-articular
injection of both corticosteroid and placebo has a small risk of the serious
adverse reaction septic arthritis. This risk of septic arthritis is varying
from 1:3000 to1:50000 in literature.
Concerns have been expressed that intra-articular corticosteroids might mask
the pain, enabling patients to prematurely mobilize and hereby promoting
further destruction of the joint. Moreover, repeated intra-articular
corticosteroid injection could lead to loss of cartilage volume due to
catabolic effects of corticosteroids.
In a recent study we found a clinical and statistical significant difference
between intra-muscular corticosteroid injection compared with placebo in
patients with hip osteoarthritis. The effect lasted at least 12 weeks. Also, an
intra-muscular injection is easier to perform than an intra-articular injection
with lesser risk of severe adverse reactions and no risk of cartilage damage.
We suspect that part of the GPs currently feel incompetent to administer
intra-articular injections due to lack of training and experience. This is why
the alternative of intra-muscular injection could increase the number of
patients with knee osteoarthritis receiving timely injections in general
practice.
Therefore, we consider an intra-muscular corticosteroid injection a valuable
and innovative treatment option for patients with knee osteoarthritis.
Additionally, if we can demonstrate clinically relevant effect after 8 to 12
weeks mid-term follow-up of a systemic corticosteroid injection for patients
with knee osteoarthritis not responding well to paracetamol/NSAIDs treatment,
GPs, orthopedic surgeons and rheumatologists will have an alternative for the
short-term effective intra-articular injection.
We hypothesize that an intra-muscular gluteal corticosteroid injection is
non-inferior to an intra-articular corticosteroid injection in reducing knee
pain measured with the KOOS 4 weeks after injection, with possibly a longer
lasting effect for at least 12 weeks.
Study objective
Primary objective: to assess whether an intra-muscular gluteal corticosteroid
injection is non-inferior to an intra-articular knee corticosteroid injection
on knee pain in patients with knee osteoarthritis in general practice at 4
weeks follow-up.
Secondary objectives:
1) What are the differences in reported adverse events frequency and
co-interventions of patients allocated to an intra-articular knee
corticosteroid injection, and to an intra-muscular gluteal corticosteroid
injection?
2) What is the non-inferiority of an intra-muscular gluteal corticosteroid
injection compared to an intra-articular knee corticosteroid injection on knee
function, OARSI/OMERACT responder criteria and perceived recovery in patients
with knee osteoarthritis at 4 weeks, and over 2, 8, 12 and 24 weeks follow-up?
Study design
The design of the study will be a pragmatic (not blinded) randomized controlled
trial with two parallel groups and a follow-up of 24 weeks after the
corticosteroid injection.
Intervention
Patients will be allocated to either intra-articular corticosteroid injection
or intramuscular corticosteroid injection.
Study burden and risks
Local infections after intramuscular injection, including cellulitis,
subcutaneous abscesses, and necrotizing fasciitis have been reported in
literature. Additionally, case reports on fatal systemic infection following
intramuscular (corticosteroid) injection have been published. Intramuscular
injection of NSAIDs is known to lead to higher risk of infection due to their
local immunosuppressive effect. An even stronger local immunosuppressive effect
can be expected after administration of corticosteroids.
In a previous RCT conducted by our research group (MEC-2011-115) about
intramuscular gluteal corticosteroid injection for hip osteoarthritis, no local
or systemic infections after intramuscular injection of corticosteroids or
placebo were observed.
Moreover, intramuscular gluteal injection can cause damage to the sciatic
nerve. This risk can be minimalized by using proper injection technique
(injection in ventrogluteal region). In the previous RCT (MEC-2011-115) no
sciatic nerve injury was reported.
Another possible risk of intramuscular injection is formation of a hematoma. To
reduce this risk, patients with coagulopathies and patients using
anticoagulants are excluded from participating in this study.
Intra-articular corticosteroid injection in any joint has a risk varying from
1:3000 to1:50000 to cause septic arthritis. However, intra-articular injection
is recommended as part of the standard care according to the NHG guideline.
Therefore, the study population will not be exposed to additional risk of
adverse reactions.
Wytemaweg 80
Rotterdam 3015 CN
NL
Wytemaweg 80
Rotterdam 3015 CN
NL
Listed location countries
Age
Inclusion criteria
1) contacted their general practitioner (consultation and/or repeat pain
medication prescription) due to knee osteoarthritis (ICPC L90 or L15 with
unequivocal diagnosis of osteoarthritis) during the past five years;
2) aged 45 years and over;
3) symptomatic knee osteoarthritis for at least 3 months prior to enrolment;
4) a minimum score of 3 on the numerical rating scale asking about the severity
of knee pain averaged over the last week (0-10; 0<=no knee pain);
5) corticosteroid injection is indicated in this patient;
6) signed informed consent form., If a patient has bilateral knee
osteoarthritis, the most painful knee according to the patient will be selected
as the study knee.
Exclusion criteria
1) use of oral corticosteroids;
2) intra-articular injection in a knee in the previous 6 months;
3) allergy to corticosteroids;
4) local or systemic infection, after recent vaccination with live attenuated
vaccine;
5) diabetes mellitus type 1, diabetes mellitus type 2 on insulin therapy,
poorly controlled diabetes mellitus type 2;
6) presence of inflammatory rheumatic diseases (such as rheumatoid arthritis,
psoriatic arthritis, spondylartropathies);
7) coagulopathy, use of anticoagulants, use of dual antiplatelet therapy;
8) a history of gastric/duodenal ulcer or a present gastric/duodenal ulcer;
9) under the care of an orthopaedic surgeon for osteoarthritis of the hip
and/or knee;
10) corticosteroid injection is not indicated in this patient;
11) unable to complete questionnaires in Dutch;
12) unable to give informed consent.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-003513-25-NL |
| CCMO | NL63816.078.17 |