Effect of bronchodilators on effort induced dyspnoea in lung hypertension patients

Phase 1

• Conditions: Idiopathic or heritable patients with pulmonary arterial hypertension (PAH).; MedDRA version: 18.1Level: PTClassification code 10064911Term: Pulmonary arterial hypertensionSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

• Registration Number: EUCTR2014-002590-10-FR
• Lead Sponsor: ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-03-02
• Last Update Posted: 8 June 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

Idiopathic or heritable PAH patients, clinically stable during the 3 preceding months, non/never smokers, with normal FEV1/VC ratio but FEF75% ? 60% predicted.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 3

Exclusion Criteria

1. Pregnant women
2. Past or current tobacco-smoking history,
3. A spirometric evidence of an obstructive ventilatory defect as defined by a reduced FEV1/VC ratio below the 5th percentile of the predicted value [43],
4. A FEF75% >60% of predicted normal values at spirometry,
5. A TLC below the 5th percentile of the predicted value [43],
6. A body mass index >30 kg.m-2,
7. Use of supplemental oxygen,
8. PAH induced by drugs and toxins,
9. PAH associated with other conditions, including connective tissue diseases, congenital heart diseases, portal hypertension, and HIV infection [42],
10. Chronic thromboembolic pulmonary hypertension [42],
11. Other respiratory, cardiac and other diseases that could contribute to dyspnoea or exercise limitation,
12. Contraindications to clinical exercise testing, such as NYHA functional class IV, syncope and others, as detailed page 28 elsewhere [26, 44].
1.NYHA functional class IV
2.Syncope
3.Acute myocardial infarction (3-5 days)
4.Unstable angina
5.Uncontrolled arrhythmias causing symptoms or hemodynamic compromise
6.Uncontrolled heart failure
7.Active endocarditis
8.Acute myocarditis or pericarditis
9.Symptomatic severe aortic stenosis
10.Suspected dissecting aneurysm
11.Acute pulmonary embolus or pulmonary infarction
12.Thrombosis of lower extremities
13.Uncontrolled asthma
14.Pulmonary edema
15.Room air desaturation at rest <85%
16.Respiratory failure
17.Acute non-cardiopulmonary disorder that may affect exercise performance or be aggravated by exercise (i.e. infection, renal failure, thyrotoxicosis)
18.Mental impairment leading to inability to cooperate

Relative Contraindications to clinical exercise testing:
Specific precision for exclusion criteria n°12: Absolute Contraindications to clinical exercise testing:
1. Left main coronary stenosis or its equivalent
2. Moderate stenotic valvular heart disease
3. Severe untreated arterial hypertension at rest (>200 mm Hg systolic, >120 mm Hg diastolic)
4. Tachyarrhythmias or bradyarrhythmias
5. High-degree atrioventricular block
6. Hypertrophic cardiomyopathy
7. Electrolyte abnormalities
8. Orthopedic impairment that compromises exercise performance
13. Specific contraindications (precautions and drug interactions) to the administration of IB or IB+SALB (please refer to section 7).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To test the hypothesis that administration of inhaled BDs (?2-agonist and/or anticholinergic), as add-ons to vasodilators, would be beneficial to PAH patients by reducing and/or delaying the rate of onset of DH-induced critical ventilatory constraints, thus ameliorating the exertional symptoms in patients with stable PAH undergoing high-intensity constant work-rate (CWR) cycle endurance test.;Secondary Objective: Difference (BD versus placebo) in CWR endurance time (60 seconds difference) will be also evaluated as potential index of improved exercise tolerance (secondary evaluation criterion).;Primary end point(s): primary endpoint: ameliorating the exertional symptoms in patients with stable PAH undergoing high-intensity constant work-rate (CWR) cycle endurance test.<br><br>secondary endpoint: potential index of improved exercise tolerance (secondary evaluation criterion).;Timepoint(s) of evaluation of this end point: LSLV

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Change (increase) of at least 60 seconds in CWR-CPET endurance time between pre-dose and post-dose BD measured at the end of CWR bouts. This criterion will be used to evaluate the potential improvement in exercise tolerance.;Timepoint(s) of evaluation of this end point: LSLV