Administrative information
Title {1} | A multicentre observational psoriatic arthritis cohort study addressing real-life outcomes of a treat to target approach in routine clinical practice. |
Trial registration {2a and 2b}. | NCT03531073 retrospectively registered 21 May 2018. |
Protocol version {3} | V6.0 28Jul2020 |
Funding {4} | Funded by National Institute for Health Research CS-2016-16-016 |
Author details {5a} | Ines Rombach, Oxford Clinical Trials Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, UK William Tillett, Royal National Hospital for Rheumatic Diseases, Bath, UK, Department of Department of Pharmacy and Pharmacology, University of Bath, UK Deepak Jadon, Department of Medicine, University of Cambridge, Cambridge, UK Laura Tucker, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, UK Marion Watson, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, UK Anne Francis, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, UK Yvonne Sinomati, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, UK Lucy Eldridge, Oxford Clinical Trials Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, UK. Melina Dritsaki, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, UK. Susan J Dutton, Oxford Clinical Trial Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, UK. Hussein Al-Mossawi, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, UK. Nicola Gullick, Rheumatology Department, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom. Ben Thompson, Department of Rheumatology, Musculoskeletal Unit, Newcastle-upon-Tyne Hospitals NHS Trust, UK Laura Coates, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford and Oxford Biomedical Research Centre, Oxford University Hospitals Trust, Oxford, UK. |
Name and contact information for the trial sponsor {5b} | University of Oxford Clinical Trials and Research Governance, Boundary Brook House, Churchill Drive, Headington, OXON, OX3 7LQ Email: ctrg@admin.ox.ac.uk |
Role of sponsor {5c} | The study sponsor provided minor input into study design and oversees data collection, management and analysis of study data. The funder has no role in study design but will review any publications prior to publication. |
Introduction
Background and rationale {6a}
Objectives {7}
Trial design {8}
Methods: participants, interventions and outcomes
Study setting {9}
Eligibility criteria {10}
Who will take informed consent? {26a}
Additional consent provisions for collection and use of participant data and biological specimens {26b}
Interventions
Explanation for the choice of comparators {6b}
Intervention description {11a}
Criteria for discontinuing or modifying allocated interventions {11b}
Strategies to improve adherence to interventions {11c}
Relevant concomitant care permitted or prohibited during the trial {11d}
Provisions for post-trial care {30}
Outcomes {12}
PASDAS calculation | (((0.18 √ physician global VAS) + (0.159 √ patient global VAS) – (0.253 x √ SF36 − physical component summary score (PCS)) + (0.101 x LN (swollen joint count + 1)) + (0.048 x LN (tender joint count + 1)) + (0.23 x LN (Leeds enthesitis index + 1)) + (0.37 LN (tender dactylitis count + 1)) + (0.102 x LN (C − reactive protein (CRP) + 1)) + 2) x 1.5. | ||
Improvement | |||
Final PASDAS score | > 1.6 | ≤ 1.6 but > 0.8 | ≤ 0.8 |
≤ 3.2 | Good | Moderate | Poor |
> 3.2 but < 5.4 | Moderate | Moderate | Poor |
≥ 5.4 | Moderate | Poor | Poor |
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Change in PsA Impact of Disease (PsAID) score [21] from baseline to 48 weeks
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Proportion achieving PsAID participant acceptable symptom state (≤ 4) [21] at 48 weeks
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Change in work productivity (WPAI-SHP) [22] (absenteeism, presenteeism and productivity loss) at 24 and 48 weeks
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Side effects reported at each time point, combined with the Treatment Satisfaction Questionnaire for Medication (TSQM)
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Outcomes at time points later than 48 weeks during the longer-term follow-up of the cohort.
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Explore immune response in patients with PsA and how this relates to clinical effectiveness with standard therapies
Procedures | Visits | |||||||
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Baseline cohort | ||||||||
Week 0 | Week 12 | Week 24 | Week 36 | Week 48 | Week 72 | Week 96 | Annually (after 96 weeks) | |
Informed consent | X | |||||||
Demographics | X | |||||||
Medical history | X | X | X | X | X | X | X | X |
Medications | X | X | X | X | X | X | X | X |
Physical examination | X | X | X | X | X | X | X | X |
Routine blood tests (FBC, U&Es, LFTs, CRP and eGFR) | X | X | X | X | X | X | X | X |
Immunology (RF, ACPA, ANA) | X | |||||||
Radiographs of hands/feet/spine | X | X | X | X | ||||
Eligibility assessment | X | |||||||
Adherence | X | X | X | X | X | X | X | |
68/66 Joint count | X | X | X | X | X | X | X | X |
Leeds and SPARCC enthesitis index | X | X | X | X | X | X | X | X |
Dactylitis count | X | X | X | X | X | X | X | X |
Psoriasis assessment (PASI and BSA) | X | X | X | X | X | X | X | X |
Physician VAS | X | X | X | X | X | X | X | X |
Metrology with BASMI (if axial involvement) | X | X | X | X | ||||
Patient questionnaires (VAS, HAQ, SF36, PsAID, WPAI, BASDAI, BASFI) | X | X | X | X | X | X | X | X |
TSQM questionnaire | X | X | X | X | X | X | X | |
EQ-5D-5L questionnaire | X | X | X | X | X | X | ||
Healthcare utilisation data | X | X | X | X | X | |||
Adverse event assessments | X | X | X | X | X | X | X | X |
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Patient reported: nausea/vomiting; heartburn/dyspepsia; diarrhoea; fatigue; hair loss; and injection site reactions
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Physician reported: infections; liver function test abnormalities; neutropenia/leucopenia; and uveitis.
Participant timeline {13}
Sample size {14}
Recruitment {15}
Assignment of interventions: allocation
Sequence generation {16a}
Concealment mechanism {16b}
Implementation {16c}
Assignment of interventions: blinding
Who will be blinded {17a}
Procedure for unblinding if needed {17b}
Data collection and management
Plans for assessment and collection of outcomes {18a}
Plans to promote participant retention and complete follow-up {18b}
Data management {19}
Confidentiality {27}
Plans for collection, laboratory evaluation and storage of biological specimens for genetic or molecular analysis in this trial/future use {33}
Statistical methods
Statistical methods for primary and secondary outcomes {20a}
Interim analyses {21b}
Methods for additional analyses (e.g. subgroup analyses) {20b}
Methods in analysis to handle protocol non-adherence and any statistical methods to handle missing data {20c}
Economic analysis
Plans to give access to the full protocol, participant level-data and statistical code {31c}
Oversight and monitoring
Composition of the coordinating centre and trial steering committee {5d}
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Monitor and supervise the progress of the study towards its interim and overall objectives,
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Review at regular intervals relevant information from other sources,
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Consider the recommendations of the DSMC,
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Inform the funding body on the progress of the study.