Prednisolone in Early Diffuse Systemic Sclerosis

NCT ID: NCT03708718

Last Updated: 2021-07-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

35 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-12-21

Study Completion Date

2021-05-27

Brief Summary

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This is a randomised placebo-controlled study of moderate dose prednisolone for 6 months in patients with early diffuse cutaneous systemic sclerosis (dcSSc). Seventy-two patients within 3 years of the onset of skin thickening will be recruited from 14 UK centres over 3 years. Co-primary end-points will be the Health Assessment Questionnaire Disability Index (HAQ-DI) and the modified Rodnan skin score (mRSS). Patients will be assessed 5 times: screening, baseline, 6 weeks, 3 and 6 months, with a code-break on exit from the study at 6 months.

Please note: From August 2020, the trial was re-started following halt due to Covid-19 as open-label. The placebo arm is the 'no treatment' arm and there is no longer a code-break at study exit.

Detailed Description

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The study is a non-commercial phase II randomised, double-blind, placebo-controlled, multi-centre study to test moderate dose prednisolone versus placebo in patients with early diffuse cutaneous systemic sclerosis (dcSSc).

Our aim is to investigate whether treatment with the steroid prednisolone is beneficial in patients with early diffuse cutaneous systemic sclerosis (also termed "scleroderma"). This is a controversial subject. Although it is very possible that prednisolone can help relieve the severe pain, itching, and disability (due to contractures and musculoskeletal involvement) of early diffuse scleroderma, doctors are often reluctant to prescribe prednisolone because of possible side effects, particularly an increased risk of serious kidney problems. Our proposed trial, treating patients with either prednisolone or placebo therapy for 6 months, should provide clinicians with a long awaited answer to the important clinical question: Can prednisolone be used as a therapy in this group of patients?

The study, funded by Arthritis Research UK, aims to determine:

1. Is moderate dose prednisolone effective in reducing pain, disability and skin thickening in patients with early diffuse scleroderma?
2. Is moderate dose prednisolone a safe therapy in patients with early diffuse scleroderma (with particular reference to kidney function)?

If the answer to both is 'yes', then prednisolone therapy will be much more widely prescribed for this patient group.

The patient population will be selected from individuals with early dcSSc, as defined by skin involvement of less than 3 years, who are considered potentially able to benefit from this treatment. Following screening, to minimise bias, eligible patients will be randomised at the baseline visit to receive either daily moderate dose prednisolone (as determined by body weight) or a matched placebo. To further eliminate subjective and unrecognised bias both the research team and patients will be blind to the randomisation. A placebo control, as opposed to an active treatment control, will be administered. This is necessary as the study treatment is adjunctive to and not a substitute for any other therapies which may be prescribed, such as immunosuppressant therapies.

Patients will attend on 5 occasions (screen, baseline, 6 weeks, 3 and 6 months). All patients will be considered off-study at the end of the 6 month visit whereupon the treatment code will be broken. At each visit a number of measurements will be taken including functional ability, degree of skin involvement (skin score), mood and kidney function. This will allow us to determine whether 'active' (prednisolone) therapy is effective and free from serious side-effects.

Please note: from August 2020, due to Covid-19 the trial was re-designed and re-started following trial halt as open-label. A placebo is no longer required. The aims, primary outcome measures and number of visits remain unchanged. However, to further mitigate the ongoing impact of Covid-19, the screen and baseline assessments may now be conducted at the same visit. Remote visits can also be carried out at 6 weeks and 6 months, if necessary.

Conditions

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Systemic Sclerosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Patients are allocated to received either prednisolone or matched placebo for the duration of the trial. The allocation is randomised 1:1.

From August 2020: Under the open-label design, patients are allocated to receive prednisolone or no additional treatment. The randomisation allocation is 1:1.
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators
Double-blind. The trial management team are blind to treatment allocation for the duration of the trial. The site research teams and patients are blind to treatment until code-break. At this point the on-site team and patient are unblind to allocation for continuing care. The site pharmacy personnel, PRedSS trial monitor and supervising statistician are unblind throughout.

From August 2020: Open-Label - The patient, site research team and site pharmacy are unblind. The trial management team are unblind for patients recruited from August 2020 onwards but remain blind to patients randomised to trial under the double-blind design. The trial monitor and trial statistician continue to be unblind for all patients randomised to trial.

Study Groups

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Prednisolone

Prednisolone 5mg enteric-coated tablets, over-encapsulated in a hard gelatine capsule and filled with lactose BP. The prednisolone will be self-administered, orally with water before or after a meal once a day. Dosing will be continuous for a total of 6 months.

The total dose prescribed will be equivalent to approximately 0.3mg/kg/day. The minimum dose prescribed will be 10mg per day (2 capsules) and a maximum of 30mg per day (6 capsules).

From August 2020: The prednisolone is no longer over-encapsulated. Prednisolone 5mg enteric-coated tablets will be prescribed and taken as above.

Group Type ACTIVE_COMPARATOR

Prednisolone 5 mg

Intervention Type DRUG

5mg prednisolone, once a day for 6 months

Placebo oral capsule; From August 2020 - 'no additional treatment'

The placebo will be a hard gelatine capsule filled with lactose BP and identically matched to the prednisolone capsules. The placebo will be self-administered once a day, orally with water before or after a meal. Dosing will be continuous for a total of 6 months.

From August 2020 - no placebo capsule will be administered.

Group Type PLACEBO_COMPARATOR

Placebo oral capsule; From August 2020 'no additional treatment'

Intervention Type DRUG

Matched placebo capsule, once a day for 6 months; From August 2020 - no additional treatment above standard of care medication

Interventions

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Prednisolone 5 mg

5mg prednisolone, once a day for 6 months

Intervention Type DRUG

Placebo oral capsule; From August 2020 'no additional treatment'

Matched placebo capsule, once a day for 6 months; From August 2020 - no additional treatment above standard of care medication

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Patients presenting with dcSSc with skin involvement extending to the proximal limb and/or trunk.
2. Male or female age ≥ 18 years.
3. Skin involvement of less than 3 years defined by patient report or clinician opinion.
4. Patient is able and willing to follow the requirements of the study.
5. Fully written informed consent.

Exclusion Criteria

1. Patients with significant uncontrolled Stage 1 Hypertension (clinic BP \>140/90mmHg i.e. either \>140mmHg OR \>90mmHg). Patients with previous hypertension which is controlled (clinic BP \<140/90mmHg) for at least 4 weeks are considered eligible.
2. Previous renal crisis or significant renal impairment (estimated Glomerular Filtration Rate (eGFR) \< 40 ml/min).
3. Patients currently on steroid therapy, or previous steroid therapy within the last 4 weeks, with the exception of inhaled steroids for respiratory diseases.
4. Patients currently participating in another randomised controlled trial of an investigational agent or device, or previous participation within the last 30 days.
5. Patients currently receiving an immunosuppressant or biologic therapy the dose of which has changed in the last 4 weeks prior to the baseline visit, or is likely to change during the first 3 months of study treatment.
6. Patients with major myositis or inflammatory arthritis. Patients with low level myositis or inflammatory arthritis are eligible for inclusion (for example, in the case of myositis, a creatine kinase less than 4 times the upper limit of normal or myositis only demonstrable on magnetic resonance imaging).
7. Female patients who are pregnant at time of screening.
8. Female patients who are breastfeeding.
9. Patients with significant inflammatory bowel disease as judged by the investigator.
10. It is important that patients do not suddenly stop taking the study medication. Patients who do not fully understand this, will be excluded.
11. Patients who are unwilling or unable to provide informed consent.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Versus Arthritis

OTHER

Sponsor Role collaborator

Prof. Ariane herrick

OTHER

Sponsor Role lead

Responsible Party

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Prof. Ariane herrick

Professor of Rheumatology

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Professor Ariane Herrick

Role: PRINCIPAL_INVESTIGATOR

University of Manchester

Locations

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Aberdeen Royal Infirmary - NHS Grampian

Aberdeen, Aberdeenshire, United Kingdom

Site Status

Addenbrooke's Hospital - Cambridge University Hospitals NHS Foundation Trust

Cambridge, Cambridgeshire, United Kingdom

Site Status

Salford Royal NHS Foundation Trust

Salford, Greater Manchester, United Kingdom

Site Status

Glasgow Royal Infirmary -

Glasgow, Lanarkshire, United Kingdom

Site Status

Aintree University Hospitals NHS Foundation Trust

Liverpool, Merseyside, United Kingdom

Site Status

Queen's Medical Centre - Nottingham University Hospitals NHS Trust

Nottingham, Nottinghamshire, United Kingdom

Site Status

Royal National Hospital For Rheumatic Diseases - Royal United Hospitals Bath NHS Foundation Trust

Bath, Somerset, United Kingdom

Site Status

Royal Hallamshire Hospital - Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield, South Yorkshire, United Kingdom

Site Status

Freeman Hospital - The Newcastle upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, Tyne and Wear, United Kingdom

Site Status

The Dudley Group NHS Foundation Trust

Dudley, West Midlands, United Kingdom

Site Status

Leeds Institute of Rheumatic and Musculoskeletal Medicine

Leeds, West Yorkshire, United Kingdom

Site Status

Southmead Hospital Bristol - North Bristol NHS Trust

Bristol, , United Kingdom

Site Status

Ninewells Hospital and Medical School - NHS Tayside

Dundee, , United Kingdom

Site Status

Royal Free London NHS Foundation Trust

London, , United Kingdom

Site Status

Countries

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United Kingdom

References

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Griffiths-Jones DJ, Garcia YS, Ryder WD, Pauling JD, Hall F, Lanyon P, Bhat S, Douglas K, Gunawardena H, Akil M, Anderson M, Griffiths B, Del Galdo F, Youssef H, Madhok R, Arthurs B, Buch M, Fligelstone K, Zubair M, Mason JC, Denton CP, Herrick AL. A Phase II randomized controlled trial of oral prednisolone in early diffuse cutaneous systemic sclerosis (PRedSS). Rheumatology (Oxford). 2023 Sep 1;62(9):3133-3138. doi: 10.1093/rheumatology/kead012.

Reference Type DERIVED
PMID: 36637209 (View on PubMed)

Other Identifiers

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119220

Identifier Type: -

Identifier Source: org_study_id

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