Magnesium Sulfate in Thrombotic Thrombocytopenic Purpura in Intensive Care

Phase 3

• Conditions: Thrombotic Thrombocytopenic Purpura
• Interventions: Drug: Placebo - Concentrate; Drug: Sulfate, Magnesium

• Registration Number: NCT03237819
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-06-13
• Study First Submitted QC: 2017-07-31
• Study First Posted: 2017-08-03
• Study Start: 2018-05-27
• Status Verified: 2021-06
• Last Update Submitted: 2021-10-28
• Last Update Posted: 2021-10-29
• Primary Completion: 2021-12-01
• Study Completion: 2021-12-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 74

Inclusion Criteria

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

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Exclusion Criteria

• Pregnancy
• No health insurance

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo - Concentrate	Glucose serum (3 ampoules)
Magnesium Sulfate	Sulfate, Magnesium	20/5000 magnesium sulfate (4 ampoules, 1,5g each)

Primary Outcome Measures

Name	Time	Method
Time to normalization of the platelet count	3 months	Normalization of the platelet is defined as a platelet count that reaches at least 150,000 per cubic millimeter for 48 consecutive hours

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Saint Louis hospital; 🇫🇷 Paris, France