Magnesium Sulfate in Thrombotic Thrombocytopenic Purpura in Intensive Care

Thrombotic Thrombocytopenic Purpura Clinical Trial

— MAGMAT  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03237819
• Other study ID #: AOR16028
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: May 27, 2018
• Est. completion date: December 1, 2021

Study information

• Verified date: June 2021
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 74
• Est. completion date: December 1, 2021
• Est. primary completion date: December 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age > or = 18 years

• Health insurance

• Signed inform consent by patient or relatives

Exclusion Criteria:

• Pregnancy

• No health insurance

Related Conditions & MeSH terms

• Purpura
• Purpura, Thrombocytopenic
• Purpura, Thrombotic Thrombocytopenic
• Thrombotic Thrombocytopenic Purpura

Intervention

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)
• 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)

Locations

Country	Name	City	State
France	Saint Louis hospital	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

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