The Use of Rituximab in Acute Thrombotic Thrombocytopenic Purpura (TTP) (NCT00937131) | Clinical Trial Compass
CompletedPhase 2
The Use of Rituximab in Acute Thrombotic Thrombocytopenic Purpura (TTP)
United Kingdom40 participantsStarted 2006-03
Plain-language summary
TTP is a rare and serious blood disorder, characterized by the formation of small clots (micro thrombi) within the circulation and can be fatal. The formation of blood clots occurs primarily in the smaller blood vessels, the arterioles and capillaries, associated with multisystem organ involvement, especially the brain and kidneys. TTP has an incidence of approximately 1-3 people/million of the population/year.
TTP is due to a decrease in an enzyme, ADAMTS 13 that is released by cells lining blood vessels (endothelial cells). ADAMTS 13 'cleaves' or breaks down very large von Willebrand Factor (vWF) strands. vWF is used in blood clotting. Deficiency or inhibition of the enzyme, results in release of the ultra large vWF into the circulation. Platelets bind to these ultra large vWF multimers, promoting blood clot formation and platelet consumption (thrombocytopenia). In more then 70% of TTP cases no precipitating cause can be found and the majority of these patients have antibodies against ADAMTS 13. Plasma Exchange (PEX) was introduced in the management of TTP in 1977 and the mortality of TTP patients has since decreased from approximately 90% to 15-20%. PEX is essential in TTP treatment as plasma contains the missing enzyme ADAMTS 13.
Rituximab (licensed and internationally used monoclonal antibody) selectively acts on white blood cells known as B-lymphocytes or B cells that produce the antibody to ADAMTS 13. By inhibiting ADAMTS 13 antibody production, ADAMTS 13 activity increases, resulting in remission. Rituximab has been used in our institutions in patients with acute TTP that are refractory to standard treatment - PEX. The resulting remission has been dramatic, with a non-toxic side effect profile and no patients to date has relapsed (longest follow-up 19 months) following Rituximab therapy. Therefore, we plan to use Rituximab with PEX in patients who present with acute TTP.
Who can participate
Age range
18 Years – 65 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion Criteria:
* Patients \> 18 years and \< 65 years who present with an acute episode of TTP
* Evidence of microangiopathic haemolytic anaemia
* Thrombocytopenia with a normal clotting screen
* Raised Lactate Dehydrogenase (one and a half time above upper normal)
* Patients without neurological dysfunction able to give informed consent
* Patients of reproductive age (must avoid pregnancy for 12 months and/or normalised B cell function after receiving Rituximab. Oestrogen containing oral contraceptive pills and the morning after pills should be avoided in female TTP patients)
* Patients with an acute deterioration in neurological function which may include encephalopathy, such as altered personality, problems with short term memory and coma can be included when consent has been given by next of kin or from the appropriate legal representative.
Exclusion Criteria:
* All female subjects who are knowingly pregnant or breast feeding or do not use an adequate form of contraception (the effect on the foetus and newborn have not yet been fully established so Rituximab should be avoided in these groups. Male patients receiving Rituximab should ensure adequate contraception for 12 months following treatment).
* Patients who are HIV positive (which does not appear to be antibody mediated, would be unlikely to benefit from Rituximab)
* Patients with childhood TTP
* Patients who have Haemolytic Uraemic Syndrome (HUS) (which is not associated with reduced ADAMTS 13 levels)
* Pati…
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
The primary objective of this study is to investigate whether Rituximab and PEX decreases the time to remission of TTP patients.