Condition category
Musculoskeletal Diseases
Date applied
15/04/2019
Date assigned
26/04/2019
Last edited
26/04/2019
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Psoriatic Arthritis (PsA) is an inflammatory arthritis estimated to occur in 15% of people with psoriasis, affecting around 150,000 people in the UK. Two-thirds of people with PsA suffer progressive joint damage with associated disability. Psoriatic arthritis causes inflammation in and around the joints. It usually affects people who already have psoriasis, a skin condition that causes a red, scaly rash. People with PsA have similar functional and quality of life impairment to rheumatoid arthritis. PsA is associated with a reduced life expectancy related to the risk of comorbidities, particularly metabolic syndrome. It is likely that some patients are overtreated with conventional ‘step up’ therapy leading to unnecessary side effects for the patient and costs to the healthcare system. This trial will investigate the feasibility and acceptability of the study design to establish whether persons with mild PsA can be managed without disease-modifying antirheumatic drugs (DMARDs).

Who can participate?
Participants with newly diagnosed PsA will be eligible if they fulfil the following criteria:
1. Oligoarthritis (<5 joints involved)
2. Low disease activity (measured by PASDAS <3.2)
3. Low impact of disease (PSAID <=4)

What does the study involve?
The study involves treating affected joints directly with glucocorticoid injections in mild disease. In this study some patients receive the usual drugs (standard care), and others are only given painkillers and steroid injections into swollen joints. This is instead of the standard treatment where at first one drug is used then two drugs together and finally newer stronger biologic drugs for patients who don’t respond to the other drugs. Injections are given as needed at 12 weekly visits up to 48 weeks. If any joint needs more than two injections in six months, patients start on the standard arthritis drugs. Patients have routine blood tests, have their joints examined and complete questionnaires at each visit. An ultrasound scan is carried out at the start of the study to see if some joints that appear normal and pain-free may actually have some inflammation.

What are the possible benefits and risks of participating?
The drugs and injections used are all in current use and have well-known safety profiles. Delaying drug therapy will delay the risk of side effects of those medications (which may include nausea/vomiting, soreness in or around the mouth, rashes, diarrhoea, hair loss [usually mild], tiredness and effects on the immune system particularly after prolonged use). The steroid injections can increase sugar levels in diabetic patients for a few days and they may increase pain in the joints for a few days. Rarely they can result in the death of a bit of bone around a joint but this tends to be at higher doses. Also rarely a joint infection may occur and need antibiotic treatment or a small operation.

Where is the study run from?
1. Cambridge University Hospitals NHS Foundation Trust
2. Royal United Hospitals Bath NHS Foundation Trust
3. Oxford University Hospitals NHS Foundation Trust

When is the study starting and how long is it expected to run for?
March 2017 to February 2023

Who is funding the study?
National Institute of Health Research (NIHR) (UK)

Who is the main contact?
Dr Marion Watson
marion.watson@ndorms.ox.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Dr Laura Coates

ORCID ID

Contact details

Botnar Research Centre
Nuffield Department of Orthopaedics
Rheumatology & Musculoskeletal Sciences
University of Oxford
Windmill Road
Oxford
OX3 7LD
United Kingdom
+44 (0)1865 737905
laura.coates@ndorms.ox.ac.uk

Additional identifiers

EudraCT number

2018-001085-42

ClinicalTrials.gov number

Nil known

Protocol/serial number

38512

Study information

Scientific title

Clinical effectiveness of symptomatic therapy compared to standard step-up care for the treatment of low impact psoriatic oligoarthritis: a 2 arm parallel group feasibility study.

Acronym

POISE

Study hypothesis

1. To determine the feasibility of conducting of a future definitive trial to establish whether a subgroup of participants with
mild PsA can be safely and effectively managed without DMARDs.
The study will assess:
1.1. The proportion of participants referred to the PsA clinic who meet the inclusion criteria (with this mild disease phenotype as defined by oligoarthritis, no poor prognostic factors and PSAID ≤4)
1.2. The proportion of participants willing to consent to the study indicating that they find the intervention acceptable
1.3. The proportion of participants not offered DMARD therapy during the 48 week trial period (DMARD therapy will be offered if participants have active disease despite 2 doses of glucocorticoids within a 6 month period)

2. To develop the design of a future definitive trial to establish whether a subgroup of patients with mild PsA can be safely
and effectively managed without DMARDs.

Ethics approval

Approved 24/05/2018, South Central- Oxford B Research Ethics Committee (Whitefriars, Level 3, Block B, Lewin's Mead, Bristol,
BS1 2NT, Tel: +44 (0)2071048058; Email: nrescommittee.southcentral-oxfordb@nhs.net), ref: 18/SC/0261

Study design

Interventional randomised parallel trial

Primary study design

Interventional

Secondary study design

Randomised parallel trial

Trial setting

Other

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Psoriatic oligoarthritis

Intervention

The trial is a randomised open-label feasibility trial with two arms:
1. Standard care
2. Symptomatic therapy

The trial forms part of a “Trials within Cohorts” or TWiCs design where participants in the cohort may be offered interventional studies subject to meeting the relevant inclusion/exclusion criteria. Consent is requested in the cohort study for data to be used without further approach.

This is a randomised open-label feasibility trial assessing the acceptability of conservative management in mild PsA and the feasibility of a future definitive trial within a cohort in a “Trials within Cohorts” or TWiCs design. A maximum of 60 participants will be recruited (30 to the cohort, arm 1 as controls and 30, arm 2 receiving the intervention). The number is an estimate, as at present it is not known how many participants with mild disease will be eligible and willing to participate. It is estimated that around 15% of participants referred with new PsA may be eligible.

Each participant will be followed for 48 weeks within this trial and will then revert to standard care within the cohort. Patients in this study will attend for study visits at baseline and weeks 12, 24, 36 and 48. Patients in the intervention arm will also be able to attend for joint injections as required in between these visits via a trial helpline. At all visits, patients will be assessed clinically for disease activity and will be asked to complete patient-reported outcomes. Adverse event information will be sought at each visit and recorded, assessed and reported as required by the protocol.

Data will be entered into an electronic CRF and appropriate validation checks carried out. Data will be analysed in accord with a statistical analysis plan starting with the null hypothesis that there is no difference in the proportion of participants achieving a PASDAS good response at week 24 between any of the two treatment arms. If this is significant at the 5% level further analyses will compare each intervention against the control arm.

Intervention type

Drug

Phase

Not Applicable

Drug names

Primary outcome measure

The feasibility of conducting a future definitive trial to establish whether a subgroup of participants with mild PsA can be safely and effectively managed without DMARDs.
The study will assess:
1. The proportion of participants referred to the PsA clinic who meet the inclusion criteria (with this mild disease phenotype as defined by oligoarthritis, no poor prognostic factors and PSAID ≤4)
2. The proportion of participants willing to consent to the study indicating that they find the intervention acceptable
3. The proportion of participants not offered DMARD therapy during the 48 week trial period (DMARD therapy will be offered if participants have active disease despite 2 doses of glucocorticoids within a 6 month period)

Secondary outcome measures

To help plan a future definitive study, if this feasibility study is successful, the researchers will collect data on the response to treatment as measured using the Psoriatic Arthritis Disease Activity Score (PASDAS) which is calculated from clinical assessments (disease activity visual analogue scale, swollen and tender joint counts, Leeds enthesitis index) and patient-reported items on questionnaires (SF-36) at 0, 12, 24, 36 and 48 weeks.

Overall trial start date

01/03/2017

Overall trial end date

28/02/2023

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Participants consented to the PsA inception cohort (MONITOR-PsA) and to be approached for alternate interventional therapies.
2. Participants with mild disease as defined by:
2.1 Oligoarticular disease with < 5 active joints at baseline assessment.
2.2 Low disease activity as defined by a PsA disease activity score (PASDAS) < = 3.2.
2.3 Low impact of disease as defined a PsA impact of disease (PSAID) < = 4.
3. Participant is willing and able to give informed consent for participation in the trial.
4. Male or female.
5. Aged 18 years or above.
6. Female participants of child bearing potential and male Participants whose partner is of child bearing potential must be willing to ensure that they or their partner use effective contraception during the trial and for 3 months thereafter if receiving DMARD therapy (excluding sulfasalazine).
7. Participant has clinically acceptable laboratory results within 6 weeks of enrolment:
7.1 Haemoglobin count >8.5 g/dL
7.2 White blood count (WBC) >3.5 x 109/L
7.3 Absolute neutrophil count (ANC) >1.5 x 109/L
7.4 Platelet count >100 x 109/L
7.5 ALT and alkaline phosphatase levels <3 x upper limit of normal
7.6 In the Investigator’s opinion, is able and willing to comply with all trial requirements.
7.7 Willing to allow his or her GP and consultant, if appropriate, to be notified of participation in the trial.

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 60; UK Sample Size: 60

Participant exclusion criteria

1. >=1 poor prognostic factors for psoriatic arthritis, from:
1.1 Raised C reactive protein (CRP) defined as >4g/dl for standard non-hsCRP
1.2 Radiographic damage defined as the presence of >= 1 erosion on plain radiographs of the hands and feet
1.3 Health assessment questionnaire (HAQ) score >1
2. Contraindications to non-steroidal anti-inflammatory drugs
3. Previous treatment for articular disease with synthetic DMARDs (including methotrexate, leflunomide or sulfasalazine) or biologic DMARDs (including TNF, IL12/23 or IL17 inhibitor therapies) or targeted synthetic DMARDs (PDE4 of JAK inhibitor therapies).
4. Female patient who is pregnant, breast feeding or planning pregnancy during the course of the trial.
5. Significant renal or hepatic impairment.
6. Scheduled elective surgery or other procedures requiring general anaesthesia during the trial.
7. Any other significant disease or disorder which, in the opinion of the Investigator, may either put the patients at risk because of participation in the trial, or may influence the result of the trial, or the participant’s ability to participate in the trial.
8. Patients who have participated in another research trial involving an investigational product in the past 12 weeks.

Recruitment start date

24/04/2019

Recruitment end date

31/08/2021

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Cambridge University Hospitals NHS Foundation Trust
Addenbrookes Hospital Hills Road
Cambridge
CB2 0QQ
United Kingdom

Trial participating centre

Royal United Hospitals Bath NHS Foundation Trust
Combe Park
Bath
BA1 3NG
United Kingdom

Trial participating centre

Oxford University Hospitals NHS Foundation Trust
John Radcliffe Hospital Headley Way Headington
Oxford
OX3 9DU
United Kingdom

Sponsor information

Organisation

University of Oxford

Sponsor details

Joint Research Office
Headington
Oxford
OX1 2JD
United Kingdom
-
ctrg@admin.ox.ac.uk

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

NIHR Academy; Grant Codes: NIHR-CS-2016-16-016

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

1. The researchers intend to publish the methodology of this study in a protocol paper
2. Peer reviewed scientific journals
3. Conference presentation
4. Publication on website
5. The researchers will also be working with their PPI contributors in case there are any further dissemination routes that should be pursued

IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

28/02/2024

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

26/04/2019: Trial's existence confirmed by the NIHR.