Thrombotic Thrombocytopenic Purpura
Conditions
Keywords
Thrombotic Thrombocytopenic Purpura, Intensive care
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.
Interventions
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)
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)
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, 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
Intervention model description
multicentre double-blind randomized clinical trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \> or = 18 years * Health insurance * Signed inform consent by patient or relatives
Exclusion criteria
* Pregnancy * No health insurance
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Duration and volume of plasma exchanges | 30 days | — |
| 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 | — |
| Acute kidney injury | day 30 | Kidney Disease: Improving Global Outcomes (KDIGO) score \> or = 1 |
Countries
France
Outcome results
None listed