Magnesium Sulfate in Thrombotic Thrombocytopenic Purpura in Intensive Care (MAGMAT)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Thrombotic Thrombocytopenic Purpura
• Intervention / Treatment: Drug: Placebo - Concentrate; Drug: Sulfate, Magnesium

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Paris, France, 75010
    • Saint Louis Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

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

Exclusion Criteria:

• Pregnancy
• No health insurance

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Glucose serum (3 ampoules)	Drug: Placebo - Concentrate; 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)
Experimental: Magnesium Sulfate; 20/5000 magnesium sulfate (4 ampoules, 1,5g each)	Drug: Sulfate, Magnesium; 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)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2018
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: June 13, 2017
• First Submitted That Met QC Criteria: July 31, 2017
• First Posted (Actual): August 3, 2017

Study Record Updates

• Last Update Posted (Actual): October 29, 2021
• Last Update Submitted That Met QC Criteria: October 28, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Thrombotic Thrombocytopenic Purpura; Intensive care
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Hematologic Diseases; Hemorrhage; Blood Coagulation Disorders; Skin Manifestations; Thrombocytopenia; Blood Platelet Disorders; Thrombophilia; Thrombotic Microangiopathies; Purpura; Purpura, Thrombocytopenic; Purpura, Thrombotic Thrombocytopenic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics; Membrane Transport Modulators; Anticonvulsants; Calcium-Regulating Hormones and Agents; Reproductive Control Agents; Calcium Channel Blockers; Tocolytic Agents; Magnesium Sulfate
• Other Study ID Numbers: AOR16028

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No