Essential thrombocytemia MedDRA version: 21.0 Level: PT Classification code 10015493 Term: Essential thrombocythaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: CARDIOASPIRIN - 100 MG COMPRESSE GASTRORESISTENTI30 COMPRESSE
Product Name: cardioaspirina
Product Code: [nd]
Pharmaceutical Form: Gastro-resistant tablet
INN or Proposed INN: ACIDO ACETIL
Sponsors
FONDAZIONE POLICLINICO UNIVERSITARIO AGOSTINO GEMELLI IRCCS UNIVERSITA' CATTOLICA DEL SACRO CUORE
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A patient will be eligible if all of the following criteria apply: - age between 18 and 75 years; - an ET diagnosis according to WHO 2008 criteria;2 - ongoing aspirin 100 mg daily since at least 1 month, according to the judgement of the referring Hematologist; - the patient understands and voluntarily signs an informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 240 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: A patient is not eligible if any of the following criteria apply: - platelet count >1,000,000/µL on three occasions over the 2 months before enrolment; - creatinine level >1.5 x upper limit of normal; - liver disease defined as AST and/or ALT values >3 x upper limit of normal; - BMI >35 kg/m2; - history of major bleeding that in the referring Hematologist's judgement may expose the patient to increased risk of bleeding recurrence - active cancer or cancer in complete remission from less than one year, except for treated early-stage squamous or basal cell skin carcinomas; - pregnancy or lactation; - use of non-steroidal anti-inflammatory drugs (NSAIDs) >3 times/week; - use of antiplatelet agents other than aspirin 100 mg od; - use of oral anticoagulants including vitamin K antagonists, anti-Xa or -IIa agents; - use of heparins or fondaparinux - chronic use of steroids (prednisone >5 mg/die or equivalent)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1- To investigate whether aspirin regimens based on twice or three times daily derived TXA2, without significantly affecting in vivo PGI2 biosynthesis, as compared to the standard, once daily 100 mg regimen. The comparison between aspirin 100 mg twice or 3 times daily vs. 100 mg od will test a superiority hypothesis in terms of serum TXB2 levels associated with each new regimen vs. standard treatment. PGIM comparisons will assess the non-inferiority of any multiple daily dosing vs standard od regimen. 2- To evaluate the long-term persistence of superior biochemical efficacy of an optimized, multiple daily dosing regimen of aspirin, as compared to the standard 100 mg od regimen. ;Secondary Objective: 1. Safety. The safety of the multiple daily aspirin regimen will be assessed in an exploratory fashion by recording major bleeding and clinically relevant non-major bleeding. Any thrombotic complication (major and minor) will also be recorded. These objectives will be explored in part B of the study, over 20-month treatment, with descriptive statistics. 2. Tolerability. The tolerability will be assessed in an exploratory fashion by recording: a. the gastrointestinal symptoms; b. the MPN symptom burden as scored by the MPN-SAF questionnaire modified to capture all microvascular symptoms and a pain numeric rating scale (NRS) for erythromelalgia 3. Stability over time of in vivo platelet activation, as assessed by the urinary biomarker TXM, will be e;Primary end point(s): Part A: Primary endpoints: - platelet thromboxane (TX)A2 production ex vivo, as reflected by serum TXB2 measured in samples collected in a fasting state, in the morning, before the next aspirin intake - vascular PGI2 biosynthesis in vivo, as reflected by urinary 2,3-dinor-6-keto-PGF1alfa (PGIM) excretion in a urine sample collected in the morning before the next aspirin intake. Both biomarkers will be measured at 14±2 days after randomization. Part B Primary endpoint: - long-term persi | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): A. Secondary endpoints: - urinary TXM measured at 14±2 days after randomization B. Secondary endpoints: - major bleeding and CRNMB and/or NB-UGI AE > grade 1 attributable to aspirin and/or major thrombotic complications (Appendices 1-3) - tolerability: gastrointestinal and microvascular symptoms (Appendices 4-6) - stability over time of in vivo biosynthesis of TXA2 and PGI2 as assesses by urinary TXM and PGIM excretion, respectively (measured in patients from Units 1, 2, 9), and of plasma von Willebrand Factor (vWF). These urinary metabolites will be assessed 3 times during part B. ;Timepoint(s) of evaluation of this end point: A. 14 DAYS B. UP TO 21 MOUNTHS | — |
Countries
Italy
Contacts
Public ContactArea di ematologia
FONDAZIONE POLICLINICO GEMELLI
Outcome results
None listed