MAGMAT: Magnesium Sulfate in Thrombotic Thrombocytopenic Purpura in Intensive Care

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03237819

Collaborator

(none)

Enrollment

Location

Arms

42.2

Anticipated Duration (Months)

1.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Thrombotic Thrombocytopenic Purpura	Drug: Sulfate, Magnesium Drug: Placebo - Concentrate	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

74 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

multicentre double-blind randomized clinical trialmulticentre double-blind randomized clinical trial

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

For each day of treatment, 4 ampoules of 10 ml will be distributed to the patient's nurse (4 ampoules of 1.5g of magnesium sulphate or 3 ampoules of 5% glucose as placebo). The bulbs will be labeled identically so that the blind can be maintained Moreover, in order to preserve the blind, the dosage of magnesemia should not be performed outside of a necessity judged by the clinician in charge of the patient

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

May 27, 2018

Anticipated Primary Completion Date :

Dec 1, 2021

Anticipated Study Completion Date :

Dec 1, 2021

Arms and Interventions

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)

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)

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

Pregnancy
No health insurance

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Saint Louis hospital	Paris		France	75010

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Assistance Publique - Hôpitaux de Paris

ClinicalTrials.gov Identifier:

NCT03237819

Other Study ID Numbers:

AOR16028

First Posted:

Aug 3, 2017

Last Update Posted:

Oct 29, 2021

Last Verified:

Jun 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Assistance Publique - Hôpitaux de Paris

Thrombotic Thrombocytopenic Purpura

Intensive care

Additional relevant MeSH terms:

Purpura

Purpura, Thrombocytopenic

Purpura, Thrombotic Thrombocytopenic

Magnesium Sulfate

Study Results

No Results Posted as of Oct 29, 2021