Acute effect of iloprost inhalation on pulmonary hypertension developed during exercise in Post-COVID-19 patients

Phase 1

• Conditions: Exercise-induced pulmonary hypertension after a COVID-19 infection; MedDRA version: 21.1Level: PTClassification code 10037400Term: Pulmonary hypertensionSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; MedDRA version: 24.1Level: LLTClassification code 10085867Term: Post-COVID-19 syndromeSystem Organ Class: 100000004862; MedDRA version: 24.1Level: LLTClassification code 10085868Term: Long COVID-19System Organ Class: 100000004862; Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

• Registration Number: EUCTR2022-003725-22-DE
• Lead Sponsor: Justus-Liebig-University Gießen

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-01-26
• Last Update Posted: 24 June 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 120

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

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< 60% pred., FVC < 60% pred., RV/TLC> 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

Study & Design

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