Clinical trial NCT03237819: Magnesium Sulfate in Thrombotic Thrombocytopenic Purpura in Intensive Care
Official title: Interest of Magnesium Sulfate in Thrombotic Thrombocytopenic Purpura in Intensive Care: Multicentric Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Thrombotic Thrombocytopenic Purpura
Keywords: Thrombotic Thrombocytopenic Purpura
Intensive care
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2017-08-03
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: multicentre double-blind randomized clinical trial
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Age \> or = 18 years
* Health insurance
* Signed inform consent by patient or relatives

Exclusion Criteria:

* Pregnancy
* No health insurance

Primary outcomes:
measure: Time to normalization of the platelet count
timeFrame: 3 months
Secondary outcomes:
measure: Duration and volume of plasma exchanges
timeFrame: 30 days
measure: platelet count
timeFrame: 5 days
measure: proportion of subjects with refractory TTP
timeFrame: 5 days
measure: Proportion of subjects with an exacerbation of TTP
timeFrame: 30 days
measure: Proportion of subjects with a relapse of TTP
timeFrame: 3 months
measure: Cardiac trouble frequency
timeFrame: day 30
measure: Cerebral trouble frequency
timeFrame: day 30
measure: Acute kidney injury
timeFrame: day 30
measure: Time to normalization of hemolysis marker levels
timeFrame: day 30
measure: Hospital length of stay
timeFrame: day 90
measure: Hospital mortality
timeFrame: day 90
measure: ICU length of stay
timeFrame: day 90
measure: ICU mortality
timeFrame: day 90
measure: Adverse events related to the use of magnesium sulfate
timeFrame: day 7
Other outcomes:
Locations:
city: Paris
country: France
facility: Saint Louis hospital
Study officials:
References: