Magnesium Sulfate in Thrombotic Thrombocytopenic Purpura in Intensive Care

NCT03237819 | Unknown Phase 3 DMC

• 1 other identifier: AOR16028
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

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.

Conditions

Thrombotic Thrombocytopenic Purpura

Keywords

Thrombotic Thrombocytopenic Purpura; Intensive care

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (14)

• Duration and volume of plasma exchanges

  30 days

• platelet count

  5 days

• proportion of subjects with refractory TTP

  5 days

• Proportion of subjects with an exacerbation of TTP

  30 days

• Proportion of subjects with a relapse of TTP

  3 months

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Glucose serum (3 ampoules)

Drug: Placebo - Concentrate

Magnesium Sulfate

EXPERIMENTAL

20/5000 magnesium sulfate (4 ampoules, 1,5g each)

Drug: Sulfate, Magnesium

Interventions

Sulfate, Magnesium DRUG

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)

Magnesium Sulfate

Placebo - Concentrate DRUG

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)

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Pregnancy
• No health insurance

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Saint Louis hospital

Paris, 75010, France

Location

MeSH Terms

Conditions

Purpura, Thrombotic Thrombocytopenic

Interventions

Magnesium Sulfate

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Thrombophilia; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Magnesium Compounds; Inorganic Chemicals; Sulfates; Sulfuric Acids; Sulfur Acids; Sulfur Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: multicentre double-blind randomized clinical trial

Study Record Dates

• First Submitted: June 13, 2017
• First Posted: August 3, 2017
• Study Start: May 27, 2018
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2021
• Last Updated: October 29, 2021

Record last verified: 2021-06

Locations

FR (1)