A 2-year, European Multicentre Study to Describe, Validate, and Predict Phenotypes of Knee Osteoarthritis (APPROACH)

May 31, 2022 updated by: F.P.J.G. Lafeber

A 2-year Multicentre, EU, Exploratory Study Without Therapeutic Benefit in Patients With Knee Osteoarthritis to Describe, Validate, and Predict Phenotypes of Knee Osteoarthritis by Use of Clinical, Imaging, and Biochemical (Bio)Markers.

Rationale: Despite a large and growing disease burden in osteoarthritis (OA), many pharmaceutical companies have abandoned OA drug development. This is mainly due to the lack of appropriate outcome measures that can robustly identify patients that can benefit from a specific therapy. Different phenotypes of OA may benefit from different types of treatment. Therefore, novel markers to identify selected phenotypes of osteoarthritis may encourage drug development.

Objective: To prospectively describe in detail pre-identified progressing phenotypes of patients with knee OA by use of conventional and novel clinical, imaging, and biochemical (bio)markers, and to validate and refine a predictive model for these (and new) progressing phenotypes based on these markers.

Study design: APPROACH is an exploratory, European, five-centre, 2-year prospective follow-up, cohort study, with extensive measurements. In this study patients are treated according to regular care by their own physician with no study related treatment prescribed. Study related diagnostic and/or monitoring procedures are applied to the patients.

Study population: Patients with tibiofemoral knee osteoarthritis, according to the clinical ACR classification criteria, pre-identified based on demographic (e.g. age), clinical (e.g. Pain NRS) and tissue structure (e.g. radiographic joint space width) parameters.

Main study parameters/endpoints: Joint tissue structure based on radiographs, MRI, and biochemical (bio)markers as well as symptoms (pain, function) and quality of life by questionnaires.

Secondary parameters: A multitude of (novel and conventional) clinical, imaging, and biochemical parameters related to osteoarthritis.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The participants will not have any direct benefit from their participation in this study other than that their OA is maximally diagnosed and followed in detail for up to 2 years (screening, baseline, 6 months, 12 months, 24 months).

Study Overview

Status

Completed

Conditions

Detailed Description

Patients will stay in the hospital for 4-5 hours per visit (for screening about 30 min) for physical examination, blood draw, MRI scans, radiographs of knees and hands (only at baseline and 24 months), CT scan of the knee (only at baseline and 24 months), low radiation whole body CT scan (only at baseline and 24 months), HandScan (only at baseline and 24 months), motion analysis, and performance based tests. They will be asked to fill out questionnaires about knee, hand and hip osteoarthritis, and about general health and pain. The patient council in the consortium indicated that the load is acceptable. The patient council will be involved in the execution of the study. The assumed risk is minimal for an individual patient and minimal compared to the contribution to the development of knowledge of their disease. These risks include minimal events due to blood sampling itself (such as hematoma or localized bleeding), radiation exposure by radiographic imaging techniques (with a minimal increased healthcare risk), and exposure to MRI techniques (without known risks and without use of contrast agents).

Study Type

Observational

Enrollment (Actual)

297

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France
        • Saint-Antoine hospital, AP-HP
  • Netherlands
      • Leiden, Netherlands
        • Leiden University Medical Center
      • Utrecht, Netherlands, 3584 CX
        • UMC Utrecht
  • Norway
      • Oslo, Norway
        • Diakonhjemmet Hospital
  • Spain
      • A Coruña, Spain
        • SERGAS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients with tibiofemoral knee osteoarthritis, according to the clinical ACR classification criteria, pre-identified based on demographic (e.g. age), clinical (e.g. Pain NRS) and tissue structure (e.g. radiographic joint space width) parameters.

Description

Inclusion Criteria:

  1. Informed consent obtained.
  2. Ambulatory (able to walk unassisted)
  3. At least 18 years of age
  4. Capable of understanding the study
  5. Capable of writing and reading in local language
  6. Predominantly tibiofemoral knee osteoarthritis and satisfy the clinical classification criteria of the American College of Rheumatology (ACR): Knee pain and three of the following criteria: over 50 years age, less than 30 minutes of morning stiffness, crepitus on active motion, bony tenderness, bony enlargement, or no palpable warmth.

  7. Highest probability to progress based on the algorithm based on the following parameters:

    • Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire
    • BMI (in recording height and weight)
    • Pain NRS of the index knee at the moment of the screening visit
    • Pain NRS of the index knee during the last week before the screening visit
    • Age
    • Gender
    • KIDA parameters of the index knee, based on standardized weight-bearing (KIDA) radiograph, measured < 3 months (patients with a Joint Space Width (JSW) < 2 mm of the index knee will not be included)

    Exclusion Criteria:

  8. Not being able to comply to the protocol
  9. Participating in a trial with local therapeutic intervention for index knee OA (pharmaceutical or surgical) or systemic Disease Modifying OsteoArthritic Drugs (DMOADs) or potential DMOADs treatments for OA at the same time or within the past 6 months or anticipated in the forthcoming; participation in non-interventional registries or epidemiological studies is allowed.
  10. Surgery of the index knee in the past 6 months (to avoid interferences with imaging)
  11. Scheduled or expected surgery of the index knee in the next 2 years (to avoid interferences with imaging)
  12. Pregnancy (child bearing woman) because of imaging (radiation and MRI, risks)
  13. Predominantly patellar femoral knee OA (clinical judgment)
  14. The following secondary osteoarthritis of the knee: clinically significant deformities of the lower limbs (varus >10°, valgus >10°), septic arthritis, inflammatory joint disease, gout, major chondrocalcinosis (pseudogout), Paget's disease of the bone, ochronosis, acromegaly, haemochromatosis, Wilson's disease, rheumatic symptoms due to malignancies, primary osteochondromatosis, osteonecrosis, osteochondritis dissecans, haemophilia
  15. Generalized pain syndrome, for example fibromyalgia
  16. Patients with contra indication to MRI or CT
  17. Hip replacement or expected hip replacement within 6 months
  18. Osteosynthesis material near the knee joint
  19. Self-reported severe Intervertebral disc (IVD) degeneration or facet OA

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
OA structural progression of the index knee
Time Frame: over two years
radiographic joint space width in mm
over two years
OA pain progression of the index knee
Time Frame: over two years
increase in points in Knee Osteoarthritis Outcome Score for pain (0-100; 0 worst, 100 best condition)
over two years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
OA progression of the index knee
Time Frame: over two years
structural progression (e.g. cartilage volume on MRI in mm3)
over two years
OA progression
Time Frame: over two years
structural progression (biochemical markers in units/ml in blood and urine)
over two years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

F.P.J.G. Lafeber

Collaborators

Assistance Publique - Hôpitaux de Paris
GlaxoSmithKline
Merck KGaA, Darmstadt, Germany
Diakonhjemmet Hospital
Newcastle University
Leiden University Medical Center
Institut de Recherches Internationales Servier
University of Surrey
Nordic Bioscience A/S
Complexo Hospitalario Universitario de A Coruña

Investigators

  • Study Director: Floris PJ Lafeber, PhD, UMC Utrecht

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 19, 2018

Primary Completion (Actual)

April 3, 2021

Study Completion (Actual)

December 1, 2021

Study Registration Dates

First Submitted

July 3, 2018

First Submitted That Met QC Criteria

March 19, 2019

First Posted (Actual)

March 21, 2019

Study Record Updates

Last Update Posted (Actual)

June 1, 2022

Last Update Submitted That Met QC Criteria

May 31, 2022

Last Verified

May 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • APPROACH-OA-P01

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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