PRedSS: Prednisolone in Early Diffuse Systemic Sclerosis. Version 1.0
Research type
Research Study
Full title
A Phase II Randomised Controlled Study of Oral Prednisolone in Early Diffuse Cutaneous Systemic Sclerosis
IRAS ID
215276
Contact name
Ariane Herrick
Contact email
Sponsor organisation
Research Governance and Integrity, University of Manchester
Eudract number
2016-002651-25
Duration of Study in the UK
3 years, 6 months, 7 days
Research summary
Research Summary
A Phase II Randomised Controlled Study of Oral Prednisolone in Early Diffuse Cutaneous Systemic Sclerosis \n\nOur 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?\n\nThe study, funded by Arthritis Research UK, aims to determine:\n1. Is moderate dose prednisolone effective in reducing pain, disability and skin thickening in patients with early diffuse scleroderma?\n2. Is moderate dose prednisolone a safe therapy in patients with early diffuse scleroderma (with particular reference to kidney function)?\n\nIf the answer to both is ‘yes’, then prednisolone therapy will be much more widely prescribed for this patient group.\n\nThis randomised controlled trial will recruit 72 patients with early diffuse scleroderma (i.e. having skin involvement for less than 3 years) over a 3 year period. The patients will receive 6 months treatment with either moderate dose prednisolone (36 patients) or matched placebo (36 patients). Patients will be recruited from up to 13 UK centres, and attend on 5 occasions (screen, baseline, 6 weeks, 3 and 6 months). At each visit a number of measurements will be taken including functional ability, degree of skin involvement (skin score), mood and kidney function, allowing us to determine whether ‘active’ (prednisolone) therapy is effective and free from serious side effects.
Summary of Results
It is not clear if steroids should be prescribed in patients with early diffuse cutaneous systemic sclerosis. Diffuse cutaneous systemic sclerosis is a painful and devastating illness with a very major impact on quality of life and survival, with only 52% to 62% of patients surviving 10 years after diagnosis. Currently there is no cure. The impact on quality of life is substantial with patients suffering from tight and itchy skin, pain, stiffness, disability, disfigurement, fatigue and often a feeling of helplessness. These symptoms are likely to be helped by steroid treatment. But steroids increase the risk of ‘scleroderma renal crisis’ which is a serious kidney problem usually associated with a rapid rise in blood pressure. This is potentially life-threatening in patients with systemic sclerosis. Scleroderma renal crisis occurs in approximately 20% of patients with early diffuse systemic sclerosis, usually within the first 3 to 5 years of the disease. Some doctors are often reluctant to prescribe steroid treatment because of the possible side effects, especially the increased risk to the kidneys. The PRedSS trial wanted to provide doctors with the long awaited answer to this important clinical question: Should steroids be used as a therapy in patients with systemic sclerosis?
The PRedSS trial aimed to see if moderate dose prednisolone (a steroid treatment) was safe and effective in patients with early diffuse cutaneous systemic sclerosis. Patients were recruited to the PRedSS trial by their own rheumatologist between December 2017 and January 2021. Clinicians in a total of 14 hospitals in England were involved and invited patients to take part. The trial was organised by researchers based at the University of Manchester and was funded by Versus Arthritis. The trial was sponsored by the University of Manchester.
Patients were randomised to receive either a moderate dose of prednisolone or a matching placebo (dummy) capsule for 6 months. Neither the patient nor the doctor knew which treatment the patient had been given (i.e. the study was ‘double-blind’). Due to the COVID-19 pandemic, patients taking part in the trial after August 2020 were given either a moderate dose of prednisolone or no treatment. Therefore after August both the patient and doctor knew if they were taking prednisolone or not (i.e. the study was no longer ‘blinded’). Patients had 5 study visits. A screening visit to see if the patient was eligible to take part was followed by a visit to record baseline measurements. Patients were then seen again at 6 weeks, 3 months and 6 months. At each visit a number of measurements were taken to assess functional ability, the amount of skin involvement, kidney function and how the patient was feeling. Some of this information was collected by the patient completing a set of questionnaires. These tests allowed us to see if treatment with prednisolone was effective and free from any serious side effects.
The study stopped early due to the COVID-19 pandemic and did not meet the recruitment target of 72 patients. Thirty five patients were recruited to the PRedSS trial of whom 25 were recruited before the COVID-19 pandemic. In total, 17 patients received prednisolone treatment and 18 patients received placebo (or no treatment after August 2020). The results show that functional ability and skin involvement improved with prednisolone treatment, but the improvements were not statistically significant. Patients in the prednisolone group also experienced less pain, reported feeling less helpless and had lower anxiety than the control patients at 3 months. There were no serious kidney problems reported.
The PRedSS trial faced a number of challenges given that PRedSS was a clinical trial of a steroid treatment which may increase the risk of infection from COVID-19. Due to the pandemic, fewer patients took part in the trial. Although the PRedSS trial suggested some benefit of taking moderate dose prednisolone in patients with systemic sclerosis, and goes part way to achieving its aims, a further randomised trial is needed because of the small number of patients studied.
The results of this research will now be presented to clinicians and scientists at conferences. An academic paper detailing the findings of the trial will also be published in a scientific journal. The results of the PRedSS trial will also be presented at future patient meetings and through newsletters of patient organisations.
REC name
North West - Greater Manchester South Research Ethics Committee
REC reference
17/NW/0320
Date of REC Opinion
26 Jun 2017
REC opinion
Favourable Opinion