Prophylactic Plasma Infusion Therapy for Congenital Thrombotic Thrombocytopenic Purpura

Study Overview
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Brief Summary
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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
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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?

Official Title
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Prophylactic Plasma Infusion Therapy for Congenital Thrombotic Thrombocytopenic Purpura

Conditions
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Purpura, Thrombotic Thrombocytopenic

Intervention / Treatment
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* Drug: Octaplas infusion and placebo (group 1)
* Drug: Octaplas infusion and placebo (group 2)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Octaplas infusion and placebo (group 1)<br>Active treatment with randomly assigned 400 ml octaplas intravenously 2-3 times a week and 400 ml placebo (for octaplas)intravenously 2-3 times a week over two weeks. | Drug: Octaplas infusion and placebo (group 1)<br>* 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.<br>* Other names: Human plasma;|
| Experimental: Octaplas infusion and placebo (group 2)<br>Active treatment with randomly assigned 400 ml octaplas intravenously once and 400 ml placebo (for octaplas)intravenously twice in two separate intervention weeks | Drug: Octaplas infusion and placebo (group 2)<br>* 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.<br>* Other names: Human plasma;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A composite score of clinical and biochemical signs of disease activity | 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 | 4 hours and 24 hours after intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ADAMTS13 activity half-life | Calculation of half-life of ADAMTS13 activity based on serial measurements of ADAMTS13 activity before and after plasma infusions | 4 hours and 24 hours after intervention | 
| ADAMTS13 allo-antibodies | Presence of allo-antibodies towards ADAMTS13 | At baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Infusions, Intravenous, Plasma, ADAMTS-13 protein, human