TTP - Thrombotic Thrombocytopenic Purpura
Conditions
Keywords
ADAMTS13, Thrombotic microangiopathy
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.
Interventions
None listed
Sponsors
Fondazione Luigi Villa
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
12 Years to 99 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence, type and severity of pregnancy complications in iTTP pregnant women | 6 years | — |
| Age at onset | 3 years | Age at the first acute iTTP episode in years |
| Sex | 3 years | — |
| Birth Country/Region | 3 years | — |
| Race | 3 years | — |
| Blood group | 3 years | ABO/Rh blood group |
| BMI | 3 years | Body mass index in kg/m\^2 |
| 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, drugs | 3 years | Proportion of potential triggering conditions/events/drugs occured/taken in the 3 months prior the acute iTTP episode |
| Incidence, type and severity of clinical manifestations, including: bleeding, cardiovascular, neurological, renal and systemic signs and symptoms | 3 years | Incidence, type and severity of clinical manifestations at presentation of the acute iTTP episode |
| Platelet count lactate dehydrogenase (LDH), total and indirect bilirubin, liver transaminases, creatinine, troponin | 3 years | Platelet count at presentation of the acute iTTP episode, expressed in number x 10\^9/L |
| Hemoglobin lactate dehydrogenase (LDH), total and indirect bilirubin, liver transaminases, creatinine, troponin | 3 years | Hemoglobin level at presentation of the acute iTTP episode, expressed in g/dL |
| Lactate dehydrogenase (LDH) lactate dehydrogenase (LDH), total and indirect bilirubin, liver transaminases, creatinine, troponin | 3 years | LDH level at presentation of the acute iTTP episode, expressed in IU/L |
| Creatinine lactate dehydrogenase (LDH), total and indirect bilirubin, liver transaminases, creatinine, troponin | 3 years | Creatinine level at presentation of the acute iTTP episode, expressed in mg/dL |
| Cardiac troponin | 3 years | Cardiac troponin level at presentation of the acute iTTP episode, expressed in ng/L |
| ADAMTS13 activity | 6 years | Level of functional ADAMTS13 activity expressed in IU/dL or % |
| Anti-ADAMTS13 antibodies | 6 years | Concentration or presence/absence of anti-ADAMTS13 antibodies |
| Number of daily therapeutic plasma exchange procedures | 3 years | Number of daily therapeutic plasma exchange procedures to achieve clinical response of the acute iTTP episode |
| 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 | 6 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 achieving clinical remission | 6 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. |
| Proportion of iTTP patients refractory to acute iTTP treatment | 6 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 experiencing complications during hospitalization, including: bleeding, thrombosis, neurological, renal, cardiac complications | 6 years | Proportion of patients who experience complications during the hospitalization for acute iTTP |
| Proportion of iTTP patients experiencing clinical exacerbation | 6 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 remission | 6 years | Proportion of iTTP patients achieving ADAMTS13 remission defined as ADAMTS13 activity ≥ 20% to \< LLN (partial) or ADAMTS13 activity ≥ LLN (complete). |
| 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 | 6 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 relapse | 6 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 clinical relapse | 6 years | — |
| Time to ADAMTS13 relapse | 6 years | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| iTTP incidence in Italy | 3 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). |
Countries
Italy
Contacts
Primary ContactSandra Maccarone
Backup ContactIlaria Mancini, MSc, PhD
Outcome results
None listed