Early Predictive Factors of Cardiac and Cerebral Involvement in TMA (MATRISK)

Identification of Early Predictive Factors of Cardiac and Cerebral Involvement in Thrombotic Microangiopathies

The aim of this study is to determine the frequency of cardiac and cerebral involvements in patients with idiopathic thrombotic microangiopathies on diagnosis. Patients will be assessed for cardiac involvement (troponin Ic level and cardiac ultrasonography) and cerebral involvement (cerebral MRI). The investigators will assess whether serum troponin Ic on diagnosis can predict morbidity and mortality of patients with a thrombotic microangiopathy at the acute phase.

The primary outcome measurement is the event free survival at day 30, as defined by death, myocardial ischemia, arrhythmia, severe cerebral injury and disease exacerbation. An increase in troponin Ic on diagnosis is defined as at least one result above 0.2 ng/ml among the three daily analyses performed after TMA diagnosis.

Study Overview

• Status: Completed
• Conditions: Thrombotic Microangiopathies; Thrombotic Thrombocytopenic Purpura
• Intervention / Treatment: Other: Biological and imaging investigations

Detailed Description

After TMA diagnosis, patients will be treated in emergency according to standard National recommendations. Patient will be included in the study as soon as the diagnosis of TMA is performed.

From day 1 to day 3, specific blood tests will be performed (serum troponin Ic and brain natriuretic peptide [BNP]). A cardiac ultrasonography within the 4 first days and a cerebral MRI within the first 7 days after TMA diagnosis will be performed.

Our hypothesis is that an increased serum troponin Ic level on diagnosis (> 0.2 ng/ml) is a predictive feature of cardiac events or worsening at the acute phase.

At 6 months, a control cardiac ultrasonography and cerebral MRI will be performed in patients with cardiac and/or cerebral involvement on diagnosis.

122 patients are expected to be included among 30 recruiting centres in France. The total duration of inclusions is 2.5 years, and the total duration of the study is of 3 years.

• Study Type: Interventional
• Enrollment (Actual): 119
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Paris, France, 75012
    • Saint Antoine

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:

• A diagnosis of thrombotic microangiopathy on the following criteria :
• A microangiopathic haemolytic anaemia (Hb< 12 g/dl, with presence of schistocytes on blood smear);
• A thrombocytopenia <150 G/l;
• No associated (precipitating) disease (HIV infection, cancer, chemotherapy, transplantation) or pregnancy;
• A written consent obtained from the patient, or from a relative for patients unable to provide the informed consent (because of cerebral involvement for example);
• Affiliation at the social insurance regimen.
• Major person

Exclusion Criteria:

• A TMA associated with an associated condition: infection with HIV (HIV) in AIDS stage, , chemotherapy, malignancy, transplantation, or pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Biological investigations; From day 1 to day 3, specific blood tests will be performed (serum troponin Ic and brain natriuretic peptide [BNP]). A cardiac ultrasonography within the 4 first days and a cerebral MRI within the first 7 days after TMA diagnosis will be performed.	Other: Biological and imaging investigations; From day 1 to day 3, specific blood tests will be performed (serum troponin Ic and brain natriuretic peptide [BNP]). A cardiac ultrasonography within the 4 first days and a cerebral MRI within the first 7 days after TMA diagnosis will be performed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
30-day event-free survival	Events include death or myocardial infarction, arrhythmia, cerebral involvement and exacerbation. Serum troponin Ic is assessed daily the 3 first days following diagnosis. Cardiac ultrasonography is performed within the 4 days following diagnosis and cerebral MRI is performed within the 7 days following the diagnosis.	At 30 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Cardiac trouble frequency and type at diagnosis	From day 1 to day 3 after diagnosis
Cerebral trouble frequency and type at diagnosis	From day 1 and day 7 after diagnosis
Comparison of cerebral and cardiac trouble at diagnosis between thrombotic microangiopathies type	Baseline
Description of cardiac and cerebral sequelae at M6 and reversibility frequency of diagnosis cardiac and cerebral lesions at M6	At 6 months
Determination of cardiac and cerebral sequelae prognostic factors at M6	At 6 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Paul Coppo, MD, PhD, Assistance Publique

Study record dates

Study Major Dates

• Study Start (Actual): June 10, 2014
• Primary Completion (Actual): July 4, 2017
• Study Completion (Actual): July 30, 2017

Study Registration Dates

• First Submitted: March 24, 2014
• First Submitted That Met QC Criteria: May 8, 2014
• First Posted (Estimate): May 9, 2014

Study Record Updates

• Last Update Posted (Actual): July 25, 2019
• Last Update Submitted That Met QC Criteria: July 23, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Thrombotic microangiopathy,; haemolytic uremic syndrome,; thrombotic thrombocytopenic purpura,; ADAMTS13,; troponin,; plasma exchange.
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Immune System Diseases; Hematologic Diseases; Hemorrhage; Blood Coagulation Disorders; Skin Manifestations; Thrombocytopenia; Blood Platelet Disorders; Thrombophilia; Vascular Diseases; Purpura; Purpura, Thrombocytopenic; Purpura, Thrombotic Thrombocytopenic; Thrombotic Microangiopathies
• Other Study ID Numbers: p120118

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No