Helping Osteoarthritis Patients to Walk With NSAID

NCT ID: NCT05761015

Last Updated: 2024-07-22

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-12-14
• Study Completion Date: 2025-11-01

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

Conditions

Osteoarthritis, Knee; Osteoarthritis, Hip; Chronic Pain

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intervention

there is only one intervention arm and no control arm; the Bayesian analysis will be conducted under hypothetical estimates of superiority vs. control.

Group Type: EXPERIMENTAL

therapeutic program including intermittent drug intake and multimodal rehabilitation program

Intervention Type: DRUG

The prescribed NSAID molecule shall be chosen according to the patient's risk profile:

• gastric/duodenal risk: age >65, history of ulcer with remission, history of inflammatory event, current low-dose acetylsalicylic acid treatment ;
• cardiovascular risk (according to Agostino scale & SCORE);

The molecule with therefore be:

• no risk: niflumic acid, 250 mg per intake;
• gastric/duodenal risk only: diclofenac, 50-100 mg per intake, plus lansoprazole;
• cardiovascular risk only: ketoprofen, 50-100 mg per intake;
• double risk: ibuprofen, 200-400 mg per intake, plus lansoprazole. For the walk test, the highest dose of diclofenac or ketoprofen will be used. Then, the patient will be free to half the dose if pain relief is achieved so.

One gram of acetaminophen will be added to any NSAID intake. The number of intakes will be limited to twice a day (morning and evening) and to 10 times a week.

Interventions

therapeutic program including intermittent drug intake and multimodal rehabilitation program

The prescribed NSAID molecule shall be chosen according to the patient's risk profile:

• gastric/duodenal risk: age >65, history of ulcer with remission, history of inflammatory event, current low-dose acetylsalicylic acid treatment ;
• cardiovascular risk (according to Agostino scale & SCORE);

The molecule with therefore be:

• no risk: niflumic acid, 250 mg per intake;
• gastric/duodenal risk only: diclofenac, 50-100 mg per intake, plus lansoprazole;
• cardiovascular risk only: ketoprofen, 50-100 mg per intake;
• double risk: ibuprofen, 200-400 mg per intake, plus lansoprazole. For the walk test, the highest dose of diclofenac or ketoprofen will be used. Then, the patient will be free to half the dose if pain relief is achieved so.

One gram of acetaminophen will be added to any NSAID intake. The number of intakes will be limited to twice a day (morning and evening) and to 10 times a week.

Intervention Type: DRUG

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

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Plateforme d'Investigation Clinique, INSERM CIC1405, CHU de Clermont-Ferrand, France

UNKNOWN

Sponsor Role: collaborator

Fondation Apicil

OTHER

Sponsor Role: collaborator

Médecine Physique et Réadaptation, CHU de Clermont-Ferrand, France

UNKNOWN

Sponsor Role: collaborator

Médecine du Sport et Explorations Fonctionnelles, CHU de Clermont-Ferrand, France

UNKNOWN

Sponsor Role: collaborator

Rhumatologie, CHU de Clermont-Ferrand, France

UNKNOWN

Sponsor Role: collaborator

Direction de la Recherche Clinique et des Innovations, CHU de Clermont-Ferrand, France

UNKNOWN

Sponsor Role: collaborator

SARL BOUCHARENC, Saint-Chély d'Apcher, France

UNKNOWN

Sponsor Role: collaborator

Inserm U1107 " Neuro-Dol ", Clermont-Ferrand, France

UNKNOWN

Sponsor Role: collaborator

Université Clermont-Auvergne, France

UNKNOWN

Sponsor Role: collaborator

University Hospital, Clermont-Ferrand

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

CHU Clemront-Ferrand

Clermont-Ferrand, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Lise Laclautre

Role: CONTACT

promo_interne_drci@chu-clermontferrand.fr

04 73 75 11 95

Facility Contacts

Lise Laclautre

Role: primary

promo_interne_drci@chu-clermontferrand.fr

04 73 75 11 95

Other Identifiers

RBHP 2022 DUALE

Identifier Type: -

Identifier Source: org_study_id