Chronic AsthmaPhase 4PRINANCT01305369
The Effect of Prasugrel on Bronchial Hyperreactivity and on Markers of Inflammation in Patients With Chronic Asthma
A Phase 4 study testing Prasugrel in people with Chronic Asthma, run by University of Milan at 1 site in Italy.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 74 years
- Conditions the study is for
- Chronic Asthma
- What is being tested?
- Prasugrel
- How many people
- 26 participants
- Where
- 1 siteItaly
- Study dates
- Mar 2011to Dec 2011
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 74 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Italy1 site
Medicina 3 Ospedale San Paolo Dipartimento di Medicina Chirurgia e Odontoiatria, Università di Milano
Milan, 20142
About this study
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)
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
- Being tested
- Prasugrel
- Keywords
- ASTHMA, PLATELET RECEPTOR P2Y12, PRASUGREL, INFLAMMATION
- Medical subject headings
- Asthma, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PrasugrelDrug
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.
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: baseline and day 15 after each treatment
Secondary outcomes (3)
Changes in measurement of airway inflammation in sputum
Measured: At baseline and on day 15 after each treatment
Changes in measurement of nitric oxide expiration
Changes in measurement of nitric oxide expiration, as a surrogate marker of airway lung inflammation
Measured: At at baseline and on day 15 after each treatment
Changes in phosphorylation of platelet VASP
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
Measured: At baseline and on day 15 after each treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2011 (estimated)
- Study startMar 2011
- Primary completionDec 2011
- Study completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic AsthmaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Milan
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Marco Cattaneo, University of Milan
- Investigators
- Marco Cattaneo, MD, Principal investigator, University of Milan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01305369
- Sponsor's protocol ID
- Prina01
- Acronym
- PRINA
- Status last verified
- Mar 2012
- First submitted
- 25 Feb 2011
- Last updated
- 6 Mar 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01305369
- Acronym / sponsor ID
- PRINA / Prina01
- Conditions
- Chronic Asthma
- Keywords
- ASTHMA, PLATELET RECEPTOR P2Y12, PRASUGREL, INFLAMMATION
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- University of MilanUniversity, hospital or other
- Study start
- Mar 2011
- Primary completion
- Dec 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 28 Feb 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
Who may qualify
- Ages
- 18 to 74 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PrasugrelPatients 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. | Drug | – |
Primary outcome
Changes in airway hyper-responsiveness
Time frame: baseline and day 15 after each treatment
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
3 secondary outcomes
Changes in measurement of airway inflammation in sputum
Time frame: At baseline and on day 15 after each treatment
Changes in measurement of nitric oxide expiration
Time frame: At at baseline and on day 15 after each treatment
Changes in phosphorylation of platelet VASP
Time frame: At baseline and on day 15 after each treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2012.
Related trials for Chronic Asthma
Active, not recruitingPhase 2/3
Local Antibiotic Delivery for Community Acquired Pneumonia
Community Acquired Pneumonia (CAP)
Recruiting
THERMotherapy Against Persistent Bacterial LUNG Infections
Lung Diseases, Obstructive, Bronchiectasis
Not yet recruiting
Reducing Exposure With Air Cleaners and Technology
Asthma, COPD (Chronic Obstructive Pulmonary Disease)
RecruitingPhase 2
Rademikibart IV for Acute Asthma and COPD Exacerbation
Asthma Acute, COPD Exacerbation Acute
Not yet recruiting
Asthma Ctrl SMART Trial
Asthma in Children, Asthma Chronic
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marco Cattaneo, MD principal investigator
University of Milan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Prasugrel in people with Chronic Asthma, run by University of Milan at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Mar 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in airway hyper-responsiveness (time frame: baseline and day 15 after each treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2012.