| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Patients with moderate/high cardiovascular risk |
| Pazienti a moderato/alto rischio cardiovascolare |
|
| E.1.1.1 | Medical condition in easily understood language |
| Cardiovascular disease |
| Malattia cardiovascolare |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
To demonstrate the non inferiority of two different dosages (20 mg or 40 mg) of sublingual preparation of aspirin in comparison to the oral formulation of aspirin (100 mg) on inhibition of platelet aggregation, assessed by
1. Efficacy
a) plasma thromboxane B2
b) platelet aggregation
2. Safety
a) adverse events, with particular regards for GI symptoms
b) blood clinical laboratory parameters (haematology and biochemistry)
c) fecal occult blood
d) systolic blood pressure and diastolic blood pressure
|
Dimostrare la non inferiorità di due differenti dosaggi (20 mg o 40 mg) di acido acetilsalicilico sublinguale in confronto con la compressa orale di acido acetilsalicilico100 mg
1. Efficacia
a) misurazione di trombossano B2 plasma
b) aggregazione piastrinica
2.Sicurezza
a) Comparsa di eventi avversi, con particolare riguardo agli effetti a livello gastrointestinale
b) parametri ematici di laboratorio (ematologia clinica e di biochimica).
c) comparsa di sangue occulto nelle feci
d) pressione arteriosa sistolica e diastoilica |
|
| E.2.2 | Secondary objectives of the trial |
Efficacy
1) urinary 11-dehydro thromboxane B2
2) plasmatic and urinary 6-keto-PGF1α
|
Efficacia
1) misurazione di 11-deidro trombossano B2
2) dosaggio di 6-keto-PGF1α urinaria |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
•men or women
•age > 18 years
•moderate-high cardiovascular risk, assessed by using the SCORE system (≥1% and <10% for 10-year risk of fatal CVD), according to the European Guidelines on cardiovascular disease prevention in clinical practice
•written informed consent.
|
•Uomini e donne
•Età >18anni
•Pazienti a moderato-alto rischio cardiovascolare valutato mediante le carte del rischio SCORE (≥ 1% e <10% per 10 anni il rischio di malattia cardiovascolare fatale), secondo le linee guida europee sulla prevenzione elle malattie cardiovascolari nella pratica clinica
•Consenso informato scritto.
|
|
| E.4 | Principal exclusion criteria |
•Age < 18 years
•Positive pregnancy test (βGCH) performed at the selection visit or results not available, women who are pregnant, women who are breast-feeding, women of childbearing potential who are not using reliable methods available to avoid pregnancy
•Patients at very high or low cardiovascular risk, having a calculated SCORE ≥10%
•History of atrial fibrillation or atrial flutter
•Patient in treatment with indication to oral anticoagulants or other antithrombotic drugs
•Patient with history of hypersensitivity or intolerance with acetylsalicylic acid or other non steroidal ant-iinflammatory drugs (NSAIDs)
•Patients with any history of hereditary angioedema hereditary, idiopathic or associated with acetylsalicylic acid
•Patients with history of peptic ulcers or gastritis or history of gastrointestinal bleeding associated to acetylsalicylic acid or other non steroidal anti-inflammatory drugs (NSAIDs)
•Patients with severe gastro-intestinal tract disorders
•Patient with asthma or NSAID-precipitated bronchospasm
•Patients with known coagulation disorders or with abnormal platelet count (< 100 000 per mm3 or > 400 000 per mm3) or with other acquired causes of impaired platelet aggregation, including uremia and paraproteinemia (monoclonal gammopathy).
•Patients with haemophilia or other bleeding disorders
•Patients with myeloproliferative disorders
•Patients with severe chronic kidney disease (GFR ,30 mL/min/ 1.73 m2), using Cockcroft’s formula:
o men = (140 - age) x weight (kg)/(0.814 x creatinine level (μmol/lL)).
o women = 0.85 x [(140 - age) x weight (kg)/(0.814 x creatinine level (μmol/lL))].
•Patients with known liver disease or biliary disease (chronic hepatitis, cirrhosis, etc) or with ALAT or ASAT upper than 3 times the upper limit of normal laboratory range.
•Patient with hyperkalemia
•History of alcoholism or drug abuse.
•Patients unlikely to co-operate in the study or to comply well with treatment or with the study visits.
•Participation in another study at the same time or within the preceding 30 days, (or a longer period in accordance to the local regulations).
•History of severe disease likely to interfere with the conduct of the study, severe uncontrolled infection, evolving neoplasm.
•History of severe mental or psychiatric disorder, severe depression or history of severe depression, e.g. requiring an hospitalisation or at high risk of suicide attempt.
•Endocrine diseases: uncontrolled dys-thyroidia, Cushing’s syndrome, acromegalia, hyperparathyroidia.
•Patient with a life expectancy of less than the 15 month duration of the study in opinion to the investigator.
•Patients with HIV or taking drugs for HIV
|
•Età < ai 18 anni
•test di gravidanza positivo (βGCH), eseguito in occasione della visita di selezione o risultati non disponibili, donne incinte, donne che allattano al seno, donne in età fertile che non usano metodi disponibili affidabili per evitare una gravidanza
•I pazienti ad elevato o basso rischio cardiovascolare con un punteggio calcolato ≥ 10% e <1% rispettivamente mediante le carte del rischio SCORE
•Storia di fibrillazione atriale o flutter striale
•pazienti in trattamento con l'indicazione ad assumere terapia con anticoagulanti orali o altri farmaci antitrombotici
•Pazienti con storia di ipersensibilità o intolleranza all’acido acetilsalicilico o a altri antinfiammatori non steroidei (FANS)
•Pazienti con una storia di angioedema ereditario, idiopatico o associato con acido acetilsalicilico
•Pazienti con storia di ulcera peptica o gastrica
•Pazienti con storia di emorragia gastrointestinale associata ad acido acetilsalicilico o a altri antinfiammatori non steroidei (FANS)
•Pazienti con gravi disturbi del tratto gastro-intestinali
•Pazienti con asma o broncospasmo precipitato dall’uso di FANS
•Pazienti con disturbi della coagulazione noti o con conta piastrinica anormale (<100 000 per mm3 o > 400 000 per mm3) o con altre cause acquisite di compromissione della aggregazione piastrinica, quali uremia e paraproteinemia (gammopatia monoclonale).
•Pazienti con emofilia o altri disturbi della coagulazione
•Pazienti con disordini mieloproliferativi
•Pazienti con grave malattia renale cronica (GFR, 30 mL/min/1,73 m2), usando la formula di Cockcroft:
- uomini = (140 - età) x peso (kg) / (0,814 x livello di creatinina (mmol/l)).
- donne=0,85 x [(140-età) x peso (kg)/(0,814xlivello di creatinina (mmol/l)).
•Pazienti con malattia epato-biliare (epatite cronica, cirrosi, ecc) o con ALT o AST di 3 volte superiori il limite superiore del normale rande di laboratorio.
•Pazienti con iperkaliemia
•Storia di alcolismo o tossicodipendenza.
•Pazienti incapaci di collaborare nello studio, o di seguire adeguatamente il trattamento o le visite
dello studio
•Partecipazione in un altro studio, allo stesso tempo o entro i 30 giorni precedenti
•Storia di gravi disturbi psichici o psichiatrici, depressione grave o anamnesi di depressione grave, ad esempio richiede una ospedalizzazione o
ad alto rischio di tentativo di suicidio.
•Malattie endocrine: distiroidismo incontrollato, sindrome di Cushing, acromegalia, iperparatiroidismo
•Pazienti che, a giudizio dello sperimentatore, hanno un’aspettativa di vita inferiore alla durata dello studio ovvero 15 mesi o con gravi infezioni non controllate, o con neoplasia in evoluzione.
•Pazienti con HIV o che assumono farmaci per HIV.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The Primary Efficacy Endpoint for the trial is the change in platelet aggregation effect after 12 week of treatment, assessed by:
a) measure of plasma thromboxane B2 analyzed by EIA Biotrak systems
b) platelet aggregation tested in platelet rich plasma
|
L'endpoint primario riguarda l’ efficacia e valuta l’effetto del cambiamento dell'aggregazione piastrinica dopo 12 settimane di trattamento, mediante:
a) misura di plasma trombossano B2 analizzato mediante sistemi Biotrak EIA
b) l'aggregazione piastrinica testato in plasma ricco di piastrine
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
The Secondary Efficacy Endpoints for the trial are the changes after 12 week of treatment, of:
a) urinary 11-dehydro thromboxane B2
b) plasmatic and urinary 6-keto-PGF1α
|
Gli endpoint secondari riguardano i cambiamenti dopo 12 settimane di trattamento, di:
a) urinario di 11-deidro trombossano B2
b) plasmatico e urinario 6-cheto-PGF1α
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| 12 weeks after the INC VISIT (randomization visit) |
| 12 settimane dopo la INC VISIT (visita di randomizzazione) |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
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