Magnesium Sulfate in Thrombotic Thrombocytopenic Purpura in Intensive Care

Study Overview
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Brief Summary
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Thrombotic Thrombocytopenic Purpura (TTP) is a potentially life-threatening thrombotic microangiopathy caused by a severe deficiency of ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif member 13). Decreased ADAMTS13 activity leads to an accumulation of ultralarge von Willebrand factor (vWF) multimers which induce aggregation of platelets and microthrombi. These microthrombi may involve the brain, heart, kidneys and lead to life-threatening organ failures. In experimental models, magnesium sulfate increases cleavage of newly released vWF by ADAMTS13, decreases the endothelial secretion of ultralarge vWF and inhibits the interaction of vWF with platelets. In another thrombotic microangiopathy, magnesium sulfate has been shown to reduce the risk of seizures in women with severe pre-eclampsia. In analogy with its evidence-based therapeutic application in pre-eclampsia and based on a strong rationale for magnesium supplementation in TTP, we propose a phase 3, double blind, placebo controlled, and randomized study to evaluate the efficacy of magnesium sulfate in more rapidly restoring normal platelet counts as measure of prevention of further microvascular thrombosis in patients with Thrombotic Thrombocytopenic Purpura.

Official Title
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Interest of Magnesium Sulfate in Thrombotic Thrombocytopenic Purpura in Intensive Care: Multicentric Randomized Controlled Trial

Conditions
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Thrombotic Thrombocytopenic Purpura

Intervention / Treatment
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* Drug: Sulfate, Magnesium
* Drug: Placebo - Concentrate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > or = 18 years Health insurance Signed inform consent by patient or relatives Exclusion Criteria: Pregnancy No health insurance

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: multicentre double-blind randomized clinical trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Glucose serum (3 ampoules) | Drug: Placebo - Concentrate<br>* For each day of treatment, 4 ampoules of 10 ml will be distributed to the nurse in charge of the patient (4 ampoules of glucose 5% as placebo)<br>|
| Experimental: Magnesium Sulfate<br>20/5000 magnesium sulfate (4 ampoules, 1,5g each) | Drug: Sulfate, Magnesium<br>* Magnesium sulphate will be administered at a dose of 6g over 20 min intravenously followed by a continuous infusion of 6g / 24h for 3 days. For each day of treatment, 4 ampoules of 10 ml will be distributed to the nurse in charge of the patient (4 ampoules of 1,5g of magnesium sulfate)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to normalization of the platelet count | Normalization of the platelet is defined as a platelet count that reaches at least 150,000 per cubic millimeter for 48 consecutive hours | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration and volume of plasma exchanges |  | 30 days | 
| platelet count |  | 5 days | 
| proportion of subjects with refractory TTP | absence of platelet count doubling after 4 days of standard treatment | 5 days | 
| Proportion of subjects with an exacerbation of TTP | recurrence during the 30 days after the last daily plasma exchange | 30 days | 
| Proportion of subjects with a relapse of TTP | recurrence occurring more than 30 days after the last daily plasma exchange | 3 months | 
| Cardiac trouble frequency |  | day 30 | 
| Cerebral trouble frequency |  | day 30 | 
| Acute kidney injury | Kidney Disease: Improving Global Outcomes (KDIGO) score > or = 1 | day 30 | 
| Time to normalization of hemolysis marker levels | Lactate dehydrogenase (LDH), haptoglobin, bilirubinemia, hemoglobin | day 30 | 
| Hospital length of stay |  | day 90 | 
| Hospital mortality | 90 days after randomization | day 90 | 
| ICU length of stay |  | day 90 | 
| ICU mortality |  | day 90 | 
| Adverse events related to the use of magnesium sulfate |  | day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thrombotic Thrombocytopenic Purpura, Intensive care