Elective rituximab in TTP
Research type
Research Study
Full title
A phase IV, prospective, randomised single-blind UK multicentre non-inferiority trial of low-dose versus standard dose rituximab for prevention of relapses in acquired TTP
IRAS ID
228923
Contact name
Mari Thomas
Contact email
Sponsor organisation
University College London
Eudract number
2017-001117-86
Duration of Study in the UK
5 years, 0 months, 1 days
Research summary
Lay Summary: This clinical trial compared a lower dose of rituximab with the standard dose in people with acquired thrombotic thrombocytopenic purpura (TTP) who were in remission but at risk of relapse. Among 68 treated patient episodes, the time until further treatment was very similar between the low-dose and standard-dose groups (around 20 months in both groups), and no clear overall difference was found between the two dosing strategies. Although the study was unable to formally prove that the low dose was non-inferior to the standard dose, the results suggested comparable effectiveness, with any differences mainly appearing in the first year after treatment. Secondary outcomes, including recovery of ADAMTS13 activity, relapse rates, and B-cell recovery, were also similar between groups. Safety findings were broadly comparable, with most adverse effects being mild and no evidence that the low-dose regimen led to worse outcomes.
Acquired thrombotic thrombocytopenic purpura (TTP) is a rare condition, presenting
suddenly with no specific symptoms and signs. It affects every organ, but critically affects the heart and brain, and patients are very sick with 50% requiring intensive care. Despite intensive treatment, 10-20% of patients die.Acquired TTP is an autoimmune disease where antibodies are formed against a specific enzyme, ADAMTS13. Once recovered from TTP, up to 50% patients used to relapse. This has improved with the introduction of rituximab, a treatment that targets B cells (part of the immune system), as part of initial TTP therapy.
We know that a fall in ADAMTS13 activity in remission can be a sign of upcoming TTP relapse, and we use rituximab therapy before patients get sick to reduce the antibodies against ADAMTS13, normalize the ADAMTS13 activity and prevent potentially life-threatening relapse. Rituximab is given as four separate weekly infusions as an outpatient.
Using the UK TTP Registry group of UK centres treating TTP, we plan to carry out a study to see if low dose rituximab is as effective as the standard dose in preventing TTP relapses. If so, it may have fewer side effects and we will also look at this.
REC name
London - Westminster Research Ethics Committee
REC reference
17/LO/1055
Date of REC Opinion
19 Jul 2017
REC opinion
Further Information Favourable Opinion