Italian iTTP Registry

Italian iTTP Registry (a Prospective Observational Study)

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.

Study Overview

• Status: Recruiting
• Conditions: TTP - Thrombotic Thrombocytopenic Purpura

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.

• Study Type: Observational
• Enrollment (Estimated): 132

Contacts and Locations

• Study Contact: Name: Sandra Maccarone; Phone Number: +39 02 551 0709; Email: contact@fondazioneluigivilla.org
• Study Contact Backup: Name: Ilaria Mancini, MSc, PhD; Phone Number: +39 02 5503 5414; Email: ilaria.mancini@guest.unimi.it

Study Locations

• Italy
  • MI
    • Milan, MI, Italy, 20122
      • Recruiting
      • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Hospitalized patients with an acute event of iTTP (first event or relapse), then followed-up in outpatient clinics of the participating centers.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
iTTP patients; iTTP patients will be treated and followed-up as per standard clinical practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Age at onset	Age at the first acute iTTP episode in years	3 years
Sex		3 years
Birth Country/Region		3 years
Race		3 years
Blood group	ABO/Rh blood group	3 years
BMI	Body mass index in kg/m^2	3 years
Proportion of patients with comorbidities, including: autoimmune diseases, cancer, HIV infection, hypertension, type 2 diabetes, hypercholesterolemia, cardiovascular disease, chronic renal failure, liver disease, depression.	Proportion of iTTP patients with comorbidities	3 years
Proportion of acute iTTP episodes preceded by potential triggering factors including: infections, pregnancy, surgery, psychological trauma, vaccination, drugs	Proportion of potential triggering conditions/events/drugs occured/taken in the 3 months prior the acute iTTP episode	3 years
Incidence, type and severity of clinical manifestations, including: bleeding, cardiovascular, neurological, renal and systemic signs and symptoms	Incidence, type and severity of clinical manifestations at presentation of the acute iTTP episode	3 years
Platelet count lactate dehydrogenase (LDH), total and indirect bilirubin, liver transaminases, creatinine, troponin	Platelet count at presentation of the acute iTTP episode, expressed in number x 10^9/L	3 years
Hemoglobin lactate dehydrogenase (LDH), total and indirect bilirubin, liver transaminases, creatinine, troponin	Hemoglobin level at presentation of the acute iTTP episode, expressed in g/dL	3 years
Lactate dehydrogenase (LDH) lactate dehydrogenase (LDH), total and indirect bilirubin, liver transaminases, creatinine, troponin	LDH level at presentation of the acute iTTP episode, expressed in IU/L	3 years
Creatinine lactate dehydrogenase (LDH), total and indirect bilirubin, liver transaminases, creatinine, troponin	Creatinine level at presentation of the acute iTTP episode, expressed in mg/dL	3 years
Cardiac troponin	Cardiac troponin level at presentation of the acute iTTP episode, expressed in ng/L	3 years
ADAMTS13 activity	Level of functional ADAMTS13 activity expressed in IU/dL or %	6 years
Anti-ADAMTS13 antibodies	Concentration or presence/absence of anti-ADAMTS13 antibodies	6 years
Number of daily therapeutic plasma exchange procedures	Number of daily therapeutic plasma exchange procedures to achieve clinical response of the acute iTTP episode	3 years
Proportion of acute iTTP patients treated with rituximab		6 years
Proportion of acute iTTP patients treated with immunosuppressors other than steroids and rituximab		6 years
Proportion of iTTP patients treated with caplacizumab		3 years
Incidence, type and severity of TTP-related drugs adverse events	Incidence, type and severity of TTP-related drugs adverse events recorded during the acute iTTP episode and disease remission of iTTP patients	6 years
Proportion of iTTP patients achieving clinical remission	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.	6 years
Proportion of iTTP patients refractory to acute iTTP treatment	Proportion of iTTP patients refractory to acute iTTP treatment. Refractoriness defined as persistent thrombocytopenia and a persistently raised LDH level despite treatment.	6 years
Proportion of iTTP patients experiencing complications during hospitalization, including: bleeding, thrombosis, neurological, renal, cardiac complications	Proportion of patients who experience complications during the hospitalization for acute iTTP	6 years
Proportion of iTTP patients experiencing clinical exacerbation	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.	6 years
Proportion of iTTP patients achieving ADAMTS13 remission	Proportion of iTTP patients achieving ADAMTS13 remission defined as ADAMTS13 activity ≥ 20% to < LLN (partial) or ADAMTS13 activity ≥ LLN (complete).	6 years
Time to clinical response		6 years
Time to clinical remission		6 years
Time to ADAMTS13 remission		6 years
Proportion of iTTP patients with a clinical relapse	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.	6 years
Proportion of iTTP patients with an ADAMTS13 relapse	Proportion of iTTP patients with an ADAMTS13 relapse defined as a decrease of ADAMTS13 activity to < 20% after a partial or complete ADAMTS13 remission.	6 years
Time to clinical relapse		6 years
Time to ADAMTS13 relapse		6 years
Incidence, type and severity of pregnancy complications in iTTP pregnant women		6 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
iTTP incidence in Italy	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).	3 years

Collaborators and Investigators

• Sponsor: Fondazione Luigi Villa
• Investigators: Principal Investigator: Flora Peyvandi, MD, PhD, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2024
• Primary Completion (Estimated): May 31, 2030
• Study Completion (Estimated): May 31, 2030

Study Registration Dates

• First Submitted: March 15, 2024
• First Submitted That Met QC Criteria: April 17, 2024
• First Posted (Actual): April 19, 2024

Study Record Updates

• Last Update Posted (Actual): July 10, 2024
• Last Update Submitted That Met QC Criteria: July 9, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: ADAMTS13; Thrombotic microangiopathy
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Hematologic Diseases; Hemorrhage; Blood Coagulation Disorders; Skin Manifestations; Thrombocytopenia; Blood Platelet Disorders; Thrombophilia; Thrombotic Microangiopathies; Cytopenia; Purpura; Purpura, Thrombocytopenic; Purpura, Thrombotic Thrombocytopenic
• Other Study ID Numbers: ItaliTTP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No