The Effect of Prasugrel on Bronchial Hyperreactivity and on Markers of Inflammation in Patients With Chronic Asthma (PRINA)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Marco Cattaneo, University of Milan
ClinicalTrials.gov Identifier:
NCT01305369
First received: February 25, 2011
Last updated: March 5, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
Chronic Asthma
Drug: Prasugrel
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Effect of Prasugrel on Bronchial Hyperreactivity and on Markers of Inflammation in Patients With Chronic Asthma: a Pilot Randomised Controlled Trial (PRINA Study)

Resource links provided by NLM:


Further study details as provided by University of Milan:

Primary Outcome Measures:
  • Changes in airway hyper-responsiveness [ Time Frame: baseline and day 15 after each treatment ] [ Designated as safety issue: No ]
    Changes in airway hyper-responsiveness, recorded as reduction of FEV1 with the mannitol test induction. Mannitol is considered more specific respect to methacholine for detecting changes in airway hyper-responsiveness in asthma patients, because it mimics the normal pathophysiology of bronchial asthma, causing the release of various mediators of bronchoconstriction


Secondary Outcome Measures:
  • Changes in measurement of airway inflammation in sputum [ Time Frame: At baseline and on day 15 after each treatment ] [ Designated as safety issue: No ]
  • Changes in measurement of nitric oxide expiration [ Time Frame: At at baseline and on day 15 after each treatment ] [ Designated as safety issue: No ]
    Changes in measurement of nitric oxide expiration, as a surrogate marker of airway lung inflammation

  • Changes in phosphorylation of platelet VASP [ Time Frame: At baseline and on day 15 after each treatment ] [ Designated as safety issue: No ]
    Changes in phosphorylation of platelet VASP (Vasodilator-stimulated phosphoprotein) by ADP, measured with a flow cytometric technique, as markers of the degree of inhibition of platelet P2Y12 receptors attained in each subjects by treatment with prasugrel


Enrollment: 26
Study Start Date: March 2011
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Prasugrel
    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.
  Eligibility

Ages Eligible for Study:   18 Years to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with chronic asthma, diagnosed based on the occurrence of episodic wheezing, chest tightness and/or dyspnoea and objectively confirmed according to standard criteria, such as methacholine airway hyper-responsiveness (PC20 FEV1 < 16mg/ml) and positivity of skin test to common allergens (prick test)
  • Positivity of bronchial challenge testing with mannitol
  • Age range of 18-74 years old
  • Duration of asthma > 1 year
  • Mild and stable asthma without chronic medication, except for the use of inhaled low dose of steroids or the use of inhaled beta2-agonist on demand
  • Written informed consent

Exclusion Criteria:

  • Pregnancy/lactation
  • Active bleeding or high risk of bleeding contraindicating treatment with antiplatelet agents or anticoagulants
  • Previous TIA or stroke
  • Age ≥ 75 years old
  • Other indication for anti-platelet therapy
  • Systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg
  • Body weight < 60 Kg
  • Use of any FANS in the last 7 days
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01305369

Locations
Italy
Medicina 3 Ospedale San Paolo Dipartimento di Medicina Chirurgia e Odontoiatria, Università di Milano
Milan, Italy, 20142
Sponsors and Collaborators
University of Milan
Investigators
Principal Investigator: Marco Cattaneo, MD University of Milan
  More Information

No publications provided

Responsible Party: Marco Cattaneo, Professor, University of Milan
ClinicalTrials.gov Identifier: NCT01305369     History of Changes
Other Study ID Numbers: Prina01
Study First Received: February 25, 2011
Last Updated: March 5, 2012
Health Authority: Italy: The Italian Medicines Agency

Keywords provided by University of Milan:
ASTHMA
PLATELET RECEPTOR P2Y12
PRASUGREL
INFLAMMATION

Additional relevant MeSH terms:
Asthma
Inflammation
Bronchial Hyperreactivity
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Pathologic Processes
Prasugrel
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 19, 2014