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

NCT01305369 | Completed Phase 4

• 1 other identifier: Prina01
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Chronic Asthma

Keywords

ASTHMA; PLATELET RECEPTOR P2Y12; PRASUGREL; INFLAMMATION

Outcome Measures

Primary Outcomes (1)

• Changes in airway hyper-responsiveness

  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

  baseline and day 15 after each treatment

Secondary Outcomes (3)

• Changes in measurement of airway inflammation in sputum

  At baseline and on day 15 after each treatment

• Changes in measurement of nitric oxide expiration

  At at baseline and on day 15 after each treatment

• Changes in phosphorylation of platelet VASP

  At baseline and on day 15 after each treatment

Interventions

Prasugrel DRUG

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 Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Milan: lead

Study Sites (1)

Medicina 3 Ospedale San Paolo Dipartimento di Medicina Chirurgia e Odontoiatria, Università di Milano

Milan, 20142, Italy

Location

MeSH Terms

Conditions

Asthma; Inflammation

Interventions

Prasugrel Hydrochloride

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Marco Cattaneo, MD

  University of Milan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 25, 2011
• First Posted: February 28, 2011
• Study Start: March 1, 2011
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: March 6, 2012

Record last verified: 2012-03

Locations

IT (1)