Exercise-induced pulmonary hypertension after a COVID-19 infection MedDRA version: 21.1 Level: PT Classification code 10037400 Term: Pulmonary hypertension System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders MedDRA version: 24.1 Level: LLT Classification code 10085867 Term: Post-COVID-19 syndrome System Organ Class: 100000004862 MedDRA version: 24.1 Level: LLT Classification code 10085868 Term: Long COVID-19 System Organ Class: 100000004862
Conditions
Interventions
Trade Name: Ventavis
Pharmaceutical Form: Nebulisation solution
INN or Proposed INN: Iloprost
CAS Number: 78919-13-8
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concent
Sponsors
Justus-Liebig-University Gießen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: All inclusion criteria will be verified after the signature of the informed consent on Day 0 and before the first right heart catheter exercise phase except criterion 5, which will be checked on Day 1 after the first right heart catheter exercise phase. 1. Patient must be = 18 years old 2. Signed informed consent 3. Patients with Post-COVID-19-Syndrome (persistent dyspnea longer than 12 weeks after a COVID-19 infection) 4. Patients with non-invasive signs of manifest or exercise-induced pulmonary hypertension (PH) 5. Exercise-induced PH determined by a mPAP/CO-slope > 3 mmHg/l/min between rest and exercise. This inclusion criterion will be checked on Day 1 on the basis of the result of the first RHC exercise phase. 6. Willingness of men and women of childbearing potential to use highly effective contraceptive methods. Such methods include: • combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: o oral o intravaginal o transdermal • progestogen-only hormonal contraception associated with inhibition of ovulation: o oral o injectable o implantable • intrauterine device (IUD) • intrauterine hormone-releasing system (IUS) • bilateral tubal occlusion • vasectomised partner • sexual abstinence 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 10 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: All exclusion criteria will be verified after the signature of the informed consent on Day 0, except criterion 1, which will be checked on Day 1 after the first right heart catheter exercise phase. 1. Hypercirculation (CI> 4.0 l/min/m2) or evidence of postcapillary PH (PAWP/CO-slope> 2 mm Hg/l/min). This exclusion criterion will be checked on Day 1 on the basis of the result of the first RHC exercise phase. 2. Preexisting clinically relevant lung disease (FEV 1 40%), radiologic signs of moderate to severe pulmonary emphysema 3. Severe coronary artery disease or unstable angina (history of surgery, history of coronary intervention two years prior to inclusion), history of myocardial infarction within the last six months, uncontrolled arterial hypertension, pulmonary hypertension due to pulmonary veno-occlusive disease, severe left ventricular hypertrophy, congenital or acquired valvular defects with clinically relevant myocardial function disorders not related to pulmonary hypertension, decompensated heart insufficiency if not under close medical control, history of stroke/transitory ischemic attack with the last three months prior to inclusion, systolic blood pressure below 85 mmHg, severe arrhythmias 4. Concomitant use of specific phosphodiesterase inhibitors (e.g. sildenafil, vardenafil, or tadalafil), endothelin antagonists (e.g. ambrisentan or macitentan), or intravenous prostacyclin; inhibitors of platelet aggregation or anticoagulants. The use of these substances needs to be stopped at least 8 weeks prior to study start. 5. Inability to perform cardiopulmonary exercise testing (CPET), including temporary orthopedic problems 6. Hemoglobin < lower limit of normal (LLN) 7. Treatment with any investigational drug within 30 days prior to inclusion 8. Pregnancy or breastfeeding 9. Any known factor or disease that might interfere with treatment compliance, study conduct, or interpretation of results, incl. limited effort in spiroergometry (CPET). 10. Hypersensitivity to the active substance or any of the other ingredients 11. Situations where the effect of Ventavis® on platelets may increase the risk of bleeding (e.g. florid ulcer disease, trauma, intracranial bleeding) 12. Patients with severe impaired liver function: Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) = 3 × the upper limit of the normal range (ULN) at screening, bilirubin = 3 mg/dL at screening (except for patients with Gilbert‘s syndrome) 13. Patients with severe impaired kidney function (creatinine clearance = 30 ml/min) 14. Simultaneous participation in another clinical trial with an experimental treatment 15. Pulmonal veno-occlusive disease
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective of this study is to assess the therapeutic approach using the inhaled prostanoid iloprost (Ventavis®) in a feasibility study in patients with exercise- induced pulmonary hypertension after an infection with COVID-19. The goal is therefore to evaluate the tolerability of the drug by the patients (identify potential side-effects, which might appear upon treatment), to determine the changes in pulmonary vascular resistance under exercise and changes in exercise capacity after treatment, and to estimate the number of patients eligible for this treatment strategy in order to plan future placebo-controlled trials. The primary objective is to determine the changes in pulmonary hemodynamics after treatment with Ventavis®. ;Secondary Objective: The secondary objectives are to assess the exercise-induced changes (maximal exercise capacity, gas exchange, ventilatory efficiency), the transpulmonary gradient and the pulmonary venous congestion after treatment with Ventavis® and to assess toxicity and safety of Ventavis® treatment. ;Primary end point(s): Primary endpoint assessment: Change in pulmonary hemodynamics during exercise shown by the mPAP/CO-slope and determined by right heart catheterization (RHC);Timepoint(s) of evaluation of this end point: Day 1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoint assessment: • Change in maximal exercise capacity: VO2max, determined by spiroergometry (CPET) • Change in the pulmonary venous system: PAWP/CO-slope, determined by RHC • Change in the precapillary system: TPG/CO-slope, determined by RHC • Change in ventilation: VE/VCO2 determined by CPET • Change in gas exchange and ventilatory efficiency: AaDO2 at max. exercise, PetCO2, EQO2 at the ventilatory threshold, all determined by CPET • Toxicity and safety of Ventavis® treatment ;Timepoint(s) of evaluation of this end point: Change in maximal exercise capacity: VO2max, determined by spiroergometry (CPET): Day 3 Change in the pulmonary venous system: PAWP/CO slope, determined by RHC: Day 1 Change in the precapillary system: TPG/CO slope, determined by RHC: Day 1 Change in ventilation: VE/VCO2 determined by CPET: Day 3 Change in gas exchange and ventilatory efficiency: AaDO2 at max. exercise, PetCO2, EQO2 at the ventilatory threshold, all determined by CPET: Day 3 | — |
Countries
Germany
Contacts
Public ContactSandrine Oberwinkler
Coordinating Center for Clinical Trials of the Philipps-University Marburg
Outcome results
None listed