The Use of Rituximab in Acute Thrombotic Thrombocytopenic Purpura (TTP)

Conditions

• Thrombotic Thrombocytopenic Purpura (TTP)

Eligibility Criteria

Sex

ALL

Age

18 Years - 65 Years

Healthy Volunteers

Not accepted

Interventions

• Rituximab — DRUG
  Concentrate for solution for infusion, Intravenous use, 375mg/m2, Maximum 8 weekly infusions

Study Details

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.

Key Dates

Start date

Mar 31, 2006

Status verified

May 2023

Primary completion

Jun 30, 2010

Completion

Jun 30, 2010

Study Design

Enrollment

40 participants (actual)

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Arms

• No Intervention: no comparator

Primary Outcome Measure

The primary objective of this study is to investigate whether Rituximab and PEX decreases the time to remission of TTP patients. [ Time Frame: One year ]