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Italian iTTP Registry

Recruiting
Conditions
TTP - Thrombotic Thrombocytopenic Purpura
Registration Number
NCT06376786
Lead Sponsor
Fondazione Luigi Villa
Brief Summary

ItaliTTP is an observational, prospective, single-arm, national, multicenter, non-pharmacological cohort study aimed at better defining and understanding the natural history, disease severity, and clinical outcomes of patients with immune-mediated thrombotic thrombocytopenic purpura (iTTP) in Italy.

A minimum of 132 consecutive patients with acute iTTP (first event or relapse) will be enrolled for 3 years, with the possibility of extension, with a follow-up period of 3 years.

Detailed Description

Acquired immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening thrombotic microangiopathy characterized by episodes of thrombocytopenia, microangiopathic hemolytic anemia, and extensive microvascular thrombosis leading to multiorgan involvement. Despite advances in understanding iTTP etiology and management in the acute phase, significant gaps in knowledge about its progression, particularly during clinical remission and concerning long-term complications, persist.

ItaliTTP, a national, multicenter, observational, prospective, non-pharmacological cohort study, aims to elucidate the natural history, severity, and outcomes of iTTP in Italy. The study will enroll hospitalized iTTP patients (experiencing either initial or recurrent episodes) and follow them in outpatient settings across participating Italian centers. The study plans to include at least 132 patients of any gender, aged 12 to 99, over a three-year period, with an option for extension, and a three-year follow-up. During hospitalization and subsequent outpatient visits, participants will undergo routine clinical assessments and laboratory tests. In addition to these data, peripheral blood samples will be collected for ADAMTS13 analysis and potential future research.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
132
Inclusion Criteria
  • Patients with an acute iTTP episode (first event or relapse), defined by thrombocytopenia and microangiopathic hemolytic anemia, in the absence of alternative causes, and the presence of severe deficiency of ADAMTS13 activity (< 10 IU/dL or <10% of normal value) and anti-ADAMTS13 autoantibodies
  • Both male and female patients, aged 12 years or older
  • Patients who have signed the informed consent for the participation to the study
Exclusion Criteria
  • Patients who have not signed the informed consent for the participation to the study

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
BMI3 years

Body mass index in kg/m\^2

Race3 years
Proportion of acute iTTP patients treated with immunosuppressors other than steroids and rituximab6 years
Time to ADAMTS13 remission6 years
Blood group3 years

ABO/Rh blood group

Proportion of patients with comorbidities, including: autoimmune diseases, cancer, HIV infection, hypertension, type 2 diabetes, hypercholesterolemia, cardiovascular disease, chronic renal failure, liver disease, depression.3 years

Proportion of iTTP patients with comorbidities

Proportion of acute iTTP episodes preceded by potential triggering factors including: infections, pregnancy, surgery, psychological trauma, vaccination, drugs3 years

Proportion of potential triggering conditions/events/drugs occured/taken in the 3 months prior the acute iTTP episode

Sex3 years
Birth Country/Region3 years
Age at onset3 years

Age at the first acute iTTP episode in years

Incidence, type and severity of clinical manifestations, including: bleeding, cardiovascular, neurological, renal and systemic signs and symptoms3 years

Incidence, type and severity of clinical manifestations at presentation of the acute iTTP episode

Hemoglobin lactate dehydrogenase (LDH), total and indirect bilirubin, liver transaminases, creatinine, troponin3 years

Hemoglobin level at presentation of the acute iTTP episode, expressed in g/dL

Cardiac troponin3 years

Cardiac troponin level at presentation of the acute iTTP episode, expressed in ng/L

Platelet count lactate dehydrogenase (LDH), total and indirect bilirubin, liver transaminases, creatinine, troponin3 years

Platelet count at presentation of the acute iTTP episode, expressed in number x 10\^9/L

Number of daily therapeutic plasma exchange procedures3 years

Number of daily therapeutic plasma exchange procedures to achieve clinical response of the acute iTTP episode

Proportion of iTTP patients treated with caplacizumab3 years
Proportion of iTTP patients experiencing complications during hospitalization, including: bleeding, thrombosis, neurological, renal, cardiac complications6 years

Proportion of patients who experience complications during the hospitalization for acute iTTP

Proportion of iTTP patients experiencing clinical exacerbation6 years

Proportion of iTTP patients experiencing clinical exacerbation defined as sustained platelet count ≥ 150 × 109/L (or above the local lower limit of normal \[LLN\]) and LDH \< 1.5 times hte upper limit of normal (ULN) and no clinical evidence of new or progressive ischemic organ injury.

Proportion of iTTP patients achieving ADAMTS13 remission6 years

Proportion of iTTP patients achieving ADAMTS13 remission defined as ADAMTS13 activity ≥ 20% to \< LLN (partial) or ADAMTS13 activity ≥ LLN (complete).

Lactate dehydrogenase (LDH) lactate dehydrogenase (LDH), total and indirect bilirubin, liver transaminases, creatinine, troponin3 years

LDH level at presentation of the acute iTTP episode, expressed in IU/L

ADAMTS13 activity6 years

Level of functional ADAMTS13 activity expressed in IU/dL or %

Creatinine lactate dehydrogenase (LDH), total and indirect bilirubin, liver transaminases, creatinine, troponin3 years

Creatinine level at presentation of the acute iTTP episode, expressed in mg/dL

Anti-ADAMTS13 antibodies6 years

Concentration or presence/absence of anti-ADAMTS13 antibodies

Proportion of acute iTTP patients treated with rituximab6 years
Incidence, type and severity of TTP-related drugs adverse events6 years

Incidence, type and severity of TTP-related drugs adverse events recorded during the acute iTTP episode and disease remission of iTTP patients

Proportion of iTTP patients refractory to acute iTTP treatment6 years

Proportion of iTTP patients refractory to acute iTTP treatment. Refractoriness defined as persistent thrombocytopenia and a persistently raised LDH level despite treatment.

Proportion of iTTP patients achieving clinical remission6 years

Proportion of iTTP patients achieving clinical remission defined as sustained clinical response with either no therapeutic plasma exchange (TPE) and no anti-von Willebrand factor (VWF) therapy for ≥ 30 days or with attainment of ADAMTS13 remission, whichever occurs first.

Time to clinical relapse6 years
Incidence, type and severity of pregnancy complications in iTTP pregnant women6 years
Time to clinical response6 years
Proportion of iTTP patients with a clinical relapse6 years

Proportion of iTTP patients with a clinical relapse defined as a platelet count decrease to \< 150 × 109/L (with other causes of thrombocytopenia ruled out), with or without clinical evidence of new ischemic organ injury, after a clinical remission.

Proportion of iTTP patients with an ADAMTS13 relapse6 years

Proportion of iTTP patients with an ADAMTS13 relapse defined as a decrease of ADAMTS13 activity to \< 20% after a partial or complete ADAMTS13 remission.

Time to ADAMTS13 relapse6 years
Time to clinical remission6 years
Secondary Outcome Measures
NameTimeMethod
iTTP incidence in Italy3 years

The number of all TTP events (first events and relapses) and first TTP events will be divided by the number of people at risk multiplied by the observation time to estimate the incidence rate of iTTP events and iTTP incident cases, respectively (in persons-years).

Trial Locations

Locations (1)

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

🇮🇹

Milan, MI, Italy

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