Clinical trial NCT05761015: Helping Osteoarthritis Patients to Walk With NSAID
Official title: A Rehabilitation Walking Program With the Help of a Transient Intake of Nonsteroidal Anti-inflammatory Drug for Patients With Painful Hip/Knee Osteoarthritis - A Pilot Cohort Study With Objectives of Short Walks in the Real Life.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Osteoarthritis, Knee
Osteoarthritis, Hip
Chronic Pain
Keywords: Osteoarthritis, Knee
Osteoarthritis, Hip
pain at movement
nonsteroidal anti-inflammatory drug
acetaminophen
paracetamol
personalized medicine
pharmacovigilance
Lead sponsor: University Hospital, Clermont-Ferrand
Sponsor class: OTHER
Collaborators: name: Plateforme d'Investigation Clinique, INSERM CIC1405, CHU de Clermont-Ferrand, France
name: Fondation Apicil
name: Médecine Physique et Réadaptation, CHU de Clermont-Ferrand, France
name: Médecine du Sport et Explorations Fonctionnelles, CHU de Clermont-Ferrand, France
name: Rhumatologie, CHU de Clermont-Ferrand, France
name: Direction de la Recherche Clinique et des Innovations, CHU de Clermont-Ferrand, France
name: SARL BOUCHARENC, Saint-Chély d'Apcher, France
name: Inserm U1107 " Neuro-Dol ", Clermont-Ferrand, France
name: Université Clermont-Auvergne, France
First posted: 2023-03-09
Enrollment: 55
Sex: ALL
Minimum age (years): 50
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: cohort
Primary purpose: TREATMENT

Brief summary: There is a lack of effective analgesic treatments to help walking patients with painful hip/knee osteoarthritis. Our team therefore imagined a new strategy lying on a multimodal rehabilitation walking program with the help of a transient intake of nonsteroidal anti-inflammatory drug (NSAID). NSAIDs are indeed known to act specifically on pain at movement, but their continuous intake would induce unacceptable side effects. To optimize the benefit/risk balance, the molecule to be chosen must fit to the patient's profile, and its intake should cover only the period of interest, i.e. planned walks. Our multimodal rehabilitation program will also include physical techniques such as appropriate footwear, a patient's education aiming at reducing fear/avoidance and spotting side effects of NSAIDs, and a prescription frame to avoid any overdosing.

This clinical study is a single-center, non-randomized, open label, one-arm trial, using drugs prescribed according to their label (i.e. osteoarthritis pain), pending a reinforced monitoring of side effects.

The primary endpoint is to evaluate efficacy and tolerance of a tailored and transient administration of NSAID within a rehabilitation walking program in patients with painful hip/knee osteoarthritis.

Secondary endpoints are to evaluate the adherence to the program and the factors influencing adherence; to identify the less well tolerated conditions of treatment (one condition being one molecule for one patient profile); to identify the factors of success among a set of baseline demographic, morphometric and psychometric variables; and to study the role of central sensitization (assessed by temporal summation) on the efficacy of treatment.

Detailed description: Study schedule:

* Inclusion visit (V0): check of the eligibility criteria, explanation of the protocol, plan for a podiatric consultation, baseline questionnaires, and delivery of diary to collect efficacy outcomes.
* Observation time (4 weeks): baseline measurement of efficacy outcomes (physical activity and pain at walk), podiatric consultation and improvement of footwear (including orthosis or soles).
* Pre-intervention visit (V1) : collection of self-reported outcomes, measurement of temporal summation, 6-min walk test before and after NSAID test \*, plan for the first 6-week intervention period and delivery of diary to collect efficacy and tolerance outcomes.
* Intermediate within-intervention visit (after 6 weeks): collection of self-reported outcomes, blood sampling (biological tolerance outcomes), plan for the second 6-week intervention period and delivery of diary to collect efficacy and tolerance outcomes.
* End-of-study visit: collection of self-reported outcomes, blood sampling (biological tolerance outcomes), and collection of last efficacy outcomes (anxiety, depression, kinesiophobia, global impression of change).

  * The patient will undergo two 6-min walk tests at the pre-intervention visit, one before and one 45 min. after oral administration of the NSAID. The patient will be considered as responsive to the NSAID if one of the following criteria occurs: a 15% increase (or more) of the time-to-first pain at walk, self-defined as bothering; a 1-point decrease (or more) of pain intensity (out of 10) throughout the test; or a 15% increase (or more) of the walked distance, if this was \< 200 m at the first test. Only patients responsive to the NSAID will continue the trial.

The sequence of successes will be treated in Bayesian analyses. Sequential analyses with be conducted stepwise. At each step, the decision to stop or to keep going will be taken, until a maximum of 50 cases eligible for analysis.

* 1st step (N=20): stop for efficacy if more than 11 successes; stop for non-efficacy if less than 6 successes; continuation otherwise (20 supplementary patients);
* 2nd step (N=40): stop for efficacy if more than 17 successes; stop for non-efficacy if less than 16 successes; continuation otherwise (20 supplementary patients);
* 3rd step (N=50): efficacy if more than 21 successes; non-efficacy otherwise

Eligibility criteria: Inclusion Criteria:

* Uni- or bilateral hip or knee idiopathic osteoarthrosis (ACR criteria, Kellgren-Lawrence grade 2 or more on recent X-ray), responsible for pain since 3 at least months, and pain at walking which intensity is at least 4/10 on a numerical rating scale.
* Less than 3 relevant walks (at least 20 minutes or 1000 km) a week.
* Ability to understand and to follow the protocol, and to answer the questionnaires

Exclusion Criteria:

* Pregnancy or breastfeeding
* Legal protection
* Body weight \< 40 kg or underweight
* Body weight \>120 kg or obesity
* Unability to walk, or unability to walk without support devices (sticks, crutches, orthoses and knee pads are allowed)
* Secondary osteoarthrosis (rheumatism, septic arthritis, recent osteonecrosis, hemochromatosis, gout, acromegalia...).
* Concomitant general bone disease (Paget, Reiter...).
* Concomitant and relevant painful disease else than due to osteoarthrosis (e.g. neuropathic pain, fibromyalgia...)
* Previous recent intervention (e.g. surgery, arthroscopy, joint infiltration) expected to relief osteoarthrosis pain throughout the study period.
* Planned intervention similar to those abovementioned, during the study period.
* Recent initiation of any new analgesic treatment (including systemic steroids).
* Planned initiation of any program expected to relief osteoarthrosis pain during the study period, such as physiotherapy, cognitive behavioral therapy...).
* Planned major surgery during the study period.
* Current cancer disease.
* Immunosuppression.
* Autoimmune disease.
* Concomitant topical or systemic NSAID treatment.
* Chronic strong opioid intake.
* Concomitant insulin therapy.
* Any absolute or relevant contraindication to NSAIDs or acetaminophen, according to the French drug agency

Primary outcomes:
measure: Success
timeFrame: V1 (pre-intervention visit) + 12 weeks
Secondary outcomes:
measure: Self-declared physical activity (efficacy outcome)
timeFrame: V1 (pre-intervention visit)
measure: Self-declared physical activity (efficacy outcome)
timeFrame: V1 (pre-intervention visit) + 6 weeks
measure: Self-declared physical activity (efficacy outcome)
timeFrame: V1 (pre-intervention visit) + 12 weeks
measure: Actual physical activity (efficacy outcome)
timeFrame: V1 (pre-intervention visit)
measure: Actual physical activity (efficacy outcome)
timeFrame: V1 (pre-intervention visit)+ 6 weeks
measure: Actual physical activity (efficacy outcome)
timeFrame: V1 (pre-intervention visit) + 12 weeks
measure: Pain at walk during the two last weeks (efficacy outcome)
timeFrame: V1 (pre-intervention visit)
measure: Pain at walk during the two last weeks (efficacy outcome)
timeFrame: V1 (pre-intervention visit) + 6 weeks
measure: Pain at walk during the two last weeks (efficacy outcome)
timeFrame: V1 (pre-intervention visit)+ 12 weeks
measure: Patient's Global Impression of Change (efficacy outcome)
timeFrame: V1 (pre-intervention visit) + 12 weeks
measure: kinesiophobia (efficacy outcome)
timeFrame: V1 (pre-intervention visit) + 12 weeks
measure: level of anxious state (efficacy outcome)
timeFrame: V1 (pre-intervention visit) + 12 weeks
measure: level of depressive state (efficacy outcome)
timeFrame: V1 (pre-intervention visit)+ 12 weeks
Other outcomes:
measure: impairment of renal function (tolerance outcome)
timeFrame: V0 (inclusion)
measure: impairment of renal function (tolerance outcome)
timeFrame: V1 (pre-intervention visit) + 6 weeks
measure: impairment of renal function (tolerance outcome)
timeFrame: V1 (pre-intervention visit)+ 12 weeks
measure: impairment of liver function (tolerance outcome)
timeFrame: V0 (inclusion)
measure: impairment of liver function (tolerance outcome)
timeFrame: V1 (pre-intervention visit) + 6 weeks
measure: impairment of liver function (tolerance outcome)
timeFrame: V1 (pre-intervention visit) + 12 weeks
measure: search for anemia (tolerance outcome)
timeFrame: V0 (inclusion)
measure: search for anemia (tolerance outcome)
timeFrame: V1 (pre-intervention visit) + 6 weeks
measure: search for anemia (tolerance outcome)
timeFrame: V1 (pre-intervention visit) + 12 weeks
measure: relevant digestive event (tolerance outcome)
timeFrame: V1 (pre-intervention visit) + 6 weeks
measure: relevant digestive event (tolerance outcome)
timeFrame: V1 (pre-intervention visit) + 12 weeks
measure: bleeding event (tolerance outcome)
timeFrame: V1 (pre-intervention visit) + 6 weeks
measure: bleeding event (tolerance outcome)
timeFrame: V1 (pre-intervention visit) + 12 weeks
measure: thrombotic event (tolerance outcome)
timeFrame: V1 (pre-intervention visit) + 6 weeks
measure: thrombotic event (tolerance outcome)
timeFrame: V1 (pre-intervention visit) + 12 weeks
measure: serious adverse event (SAE) (tolerance outcome)
timeFrame: V1 (pre-intervention visit) + 6 weeks
measure: serious adverse event (SAE) (tolerance outcome)
timeFrame: V1 (pre-intervention visit) + 12 weeks
measure: EPICES scale (Evaluation of Precariousness and Health Inequalities in Health Examination Centers) (tolerance outcome)
timeFrame: V0 (inclusion)
measure: Pain Catastrophizing Scale (PCS) (tolerance outcome)
timeFrame: V0 (inclusion)
measure: Tampa Scale of Kinesiophobia (TSK) (tolerance outcome)
timeFrame: V0 (inclusion)
measure: level of anxious state (tolerance outcome)
timeFrame: V0 (inclusion)
measure: level of depressive state (tolerance outcome)
timeFrame: V0 (inclusion)
measure: temporal summation of pain (tolerance outcome)
timeFrame: V0 (inclusion ) + 4 weeks
Locations:
city: Clermont-Ferrand
country: France
facility: CHU Clemront-Ferrand
Study officials:
References: