The Effect of Prasugrel on Bronchial Hyperreactivity and on Markers of Inflammation in Patients With Chronic Asthma
Condition: Chronic Asthma
MeSH terms: Asthma; Bronchial Hyperreactivity; Inflammation
Study type: Interventional
Phase: Phase 4

Summary: 
      Cysteinyl leukotrienes (cys-LTs) are lipid inflammatory mediators that abound in mucosal
      inflammation and play a validated role in the pathogenesis of human asthma. It has recently
      been demonstrated that the platelet adenosine diphosphate (ADP) receptor, P2Y12, is required
      for LT4-mediated pulmonary inflammation and could be a novel potential therapeutic target for
      asthma. Thienopyridines (such as ticlopidine and clopidogrel) are pro-drugs, with proven
      antithrombotic efficacy, whose active metabolites selectively inhibit the platelet P2Y12
      receptors. One of the drawbacks of thienopyridines is the high inter-individual variability
      in pharmacological response, mostly due to the high inter-individual variability in the
      capacity of transforming the pro-drug in its active metabolite. Prasugrel is a new member of
      the class of thienopyridines, with faster onset of action and a more uniform inhibition of
      platelet function compared to the other thienopyridines. Primary objective of our study will
      be to test whether or not the inhibition of the platelet P2Y12 receptor by prasugrel reduces
      the bronchial hyper-reactivity in patients with chronic asthma. The investigators designed a
      randomized, double blind (Subject, Caregiver, Investigator, Outcomes Assessor), crossover,
      placebo-controlled, prospective study, which will enroll 26 patients. Randomization will be
      performed in sequential blocks. Patients will be blindly and randomly allocated to treatment
      A (prasugrel 10 mg daily) or B (placebo) for 15 days. After a 15-day wash-out period,
      patients who had initially been allocated to treatment "A" will be allocated to treatment
      "B", and vice versa. Measurements will be done at baseline and on day 15 after each
      treatment, at the same time (+/- 1 h) of the day. Primary efficacy measure will be changes in
      airway hyper-responsiveness, recorded as reduction of FEV1 using the mannitol test induction.
      Secondary efficacy measures will be changes in markers of airway inflammation in sputum,
      changes in measurement of nitric oxide expiration (as surrogate marker of airway lung
      inflammation), count of eosinophil granulocytes in peripheral blood smear, changes in asthma
      exacerbation rates and symptom scores. Changes in phosphorylation of platelet VASP
      (Vasodilator-stimulated phosphoprotein) by ADP, measured with a flow cytometric technique,
      will be used as markers of the degree of inhibition of platelet P2Y12 receptors attained in
      each subjects by treatment with prasugrel.
    


Intervention name(s): Prasugrel
Intervention type(s): Drug
Intervention description(s): Patients will be blindly and randomly allocated to treatment A (prasugrel 10 mg daily) or B (placebo) for 15 days. After a 15-day wash-out period, patients who had initially been allocated to treatment "A" will be allocated to treatment "B", and vice versa.
Intervention MeSH terms: Prasugrel Hydrochloride
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: ASTHMA; PLATELET RECEPTOR P2Y12; PRASUGREL; INFLAMMATION