Purpura, Thrombotic Thrombocytopenic
Conditions
Keywords
Infusions, Intravenous, Plasma, ADAMTS-13 protein, human
Brief summary
Congenital thrombotic thrombocytopenic purpura (TTP), also called Upshaw-Schulman Syndrome or hereditary or familial TTP is a rare, but severe disease. The purpose of this study is to determine how infusions of plasma to patients with congenital TTP correlate with symptoms and signs of activity of the disease, and to determine why some patients need more frequent infusions of plasma than others to prevent acute attacks of the disease.
Detailed description
Patients with congenital TTP have an inherited lack of function or amount of a protein in plasma called ADAMTS13, that otherwise is responsible for cleaving large von Willebrand-molecules into smaller parts. The patients suffer recurrent attacks of clotting of small blood vessels, that can cause damage to major organs, including the central nervous system. Acute attacks can be treated successfully with infusions of human plasma, and some patients also receive regular plasma therapy for prevention of acute attacks. A small group of patients receive preventive plasma infusions twice or more weekly, indicating a much higher need for plasma than what is otherwise recommended for preventive therapy. Do these patients have an ongoing activity of their disease despite a stimulus? Or a higher turn-over of transfused ADAMTS13? Have these patients developed antibodies against transfused ADAMTS13? Are any symptoms correlated with signs of disease activity?
Interventions
DRUGOctaplas infusion and placebo (group 1)
Intervention period is Monday-Friday in two following weeks. Active treatment with Octaplas is given 2-3 times each week and placebo is given the other 2-3 days of intervention each week. Route of administration is intravenously.
DRUGOctaplas infusion and placebo (group 2)
Intervention period is Monday-Wednesday in two separate weeks (minimum of three weeks between intervention weeks). Active treatment with Octaplas is given once and placebo is given twice each week. Route of administration is intravenously.
Sponsors
Norwegian University of Science and Technology
St. Olavs Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of congenital TTP * On regular prophylactic plasma treatment: \> Once weekly (group 1) or \>1 \<3 times monthly (group 2) * Between 18 and 65 years * Capable of understanding and complying with the protocol
Exclusion criteria
* Pregnancy * Acute bout of TTP requiring daily plasma infusions or -exchange for more than 3 days, within the last 2 weeks before intervention period
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| A composite score of clinical and biochemical signs of disease activity | 4 hours and 24 hours after intervention | Biochemical signs of disease activity are scored by measurements of lactate dehydrogenase, hemoglobin, platelet counts and ADAMTS13 activity. Clinical signs of disease activity are measured by an evaluator's score and subjects symptom screening |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ADAMTS13 activity half-life | 4 hours and 24 hours after intervention | Calculation of half-life of ADAMTS13 activity based on serial measurements of ADAMTS13 activity before and after plasma infusions |
| ADAMTS13 allo-antibodies | At baseline | Presence of allo-antibodies towards ADAMTS13 |
Outcome results
None listed