Effect of bronchodilators on effort induced dyspnoea in lung hypertension patients

• Register: EUCTR
• Last refreshed on: 8 June 2020
• Main ID: EUCTR2014-002590-10-FR
• Date of registration: 02/03/2016
• Prospective Registration: No
• Primary sponsor: ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)
• Public title: Effect of bronchodilators on effort induced dyspnoea in lung hypertension patients
• Scientific title: Effect of bronchodilators on effort induced dyspnoea in patients suffering lung hypertension - BD-HTAP
• Date of first enrolment: 11/02/2016
• Target sample size: 18
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-002590-10
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: yes; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: yes; Other specify the comparator: Physiological serum; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

France

Contacts

• Name: DRCD Hôpital St Louis
• Affiliation: ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)

• Name: DRCD Hôpital St Louis
• Affiliation: ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)

Key inclusion & exclusion criteria

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).



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Idiopathic or heritable patients with pulmonary arterial hypertension (PAH).
MedDRA version: 18.1 Level: PT Classification code 10064911 Term: Pulmonary arterial hypertension System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Intervention(s)

Trade Name: Bromure d'Ipratropium
Product Name: Bromure d'Ipratropium
Pharmaceutical Form: Nebuliser solution
INN or Proposed INN: Bromure d'Ipratropium
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 0.5mg/2ml-
Pharmaceutical form of the placebo: Inhalation vapour, liquid
Route of administration of the placebo: Inhalation use

Trade Name: Salbutamol
Product Name: Salbutamol
Pharmaceutical Form: Nebuliser solution
INN or Proposed INN: Salbutamol
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5mg/2.5ml-
Pharmaceutical form of the placebo: Inhalation vapour, liquid
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: LSLV

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.

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.

secondary endpoint: potential index of improved exercise tolerance (secondary evaluation criterion).

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).

Secondary Outcome(s)

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

Secondary ID(s)

P130906

Source(s) of Monetary Support

DGOS

Ethics review

Status: Approved
Approval date: 08/02/2019
Contact: