Pulmonary Vascular Dysfunction as a Cause of Persistent Exertional Dyspnea After Coronavirus Disease (COVID-19)

COVID-19 Clinical Trial

— PulmVasC  

Official title:

Pulmonary Vascular Dysfunction as a Cause of Persistent Exertional Dyspnea After COVID-19 (PulmVasC)- A Multicenter, Prospective Cohort/Observational Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05374577
• Other study ID #: KKS-300
• Status: Recruiting
• Start date: April 15, 2022
• Est. completion date: June 2025

Study information

• Verified date: May 2024
• Source: University of Giessen
• Contact: Natascha Sommer, PD
• Phone: +0049-(0641)985 56742
• Email: Natascha.Sommer[@]innere.med.uni-giessen.de
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

To identify pulmonary vascular disease in post/long-COVID-19 patients as a cause of dyspnea/exercise limitation and to differentiate it from other causes of dyspnea

Description:

The aim is to identify pulmonary vascular disease in post/long-COVID-19 patients as a cause of dyspnea/exercise limitation and to differentiate it from other causes of dyspnea (muscular, left cardiac, psychological, deconditioning-related causes) by investigating ventilation-perfusion (V/Q) mismatch and (exercise-induced) pulmonary hypertension (PH) or right heart dysfunction.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: June 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age = 18 years, patients with a suspected diagnosis of post/long-COVID-19 syndrome who present to our pneumology or infectious disease outpatient clinic or corresponding ward from the start of the study and whose SARS-CoV-2 infection was diagnosed at least 3 and not longer than 18 months prior to presentation

• Patients at least 3 and not longer than 18 months after a SARS-CoV-2 infection without post/long-COVID-19 syndrome who present to our post-infection outpatient clinic for follow-up

Exclusion Criteria:

• Patients who refuse to participate in the study

• Severe underlying chronic pulmonary, cardiac, or systemic disease (e.g., Chronic obstructive pulmonary disease (COPD), severe heart failure, neuromuscular disease) that was diagnosed prior to acute COVID-19 disease and whose progression appears likely as the cause of dyspnea

• Other non pneumologic causes of dyspnea (e.g., hemoglobin < 100 g/L)

• Unstable or acute disease (e.g., acute infection, acute renal failure, acute coronary syndrome)

• Inability to perform spiroergometry, including transient orthopedic problems, contraindications to central venous and arterial catheter placement (e.g., severe bleeding tendency).

Related Conditions & MeSH terms

• COVID-19
• Dyspnea

Intervention

Other:
• pulmonary vascular dysfunction
Right ventricular function determined by echocardiography at rest and during exercise (non-invasive estimation of ventilation-perfusion mismatch), systemic endothelial function, left heart function, and plasma levels of vasoactive biomarkers compared with clinical parameters of dyspnea and exercise capacity. Further examinations will be performed in patients with still unclear cause of persistent shortness of breath after 3 months of follow-up (subgroup RHC)
• pulmonary vascular function
Right ventricular function determined by echocardiography at rest and during exercise (non-invasive estimation of ventilation-perfusion mismatch), systemic endothelial function, and plasma levels of vasoactive biomarkers compared with clinical parameters of dyspnea and exercise capacity.

Locations

Country	Name	City	State
Germany	Natascha Sommer	Giessen

Sponsors (1)

Lead Sponsor	Collaborator
University of Giessen

Country where clinical trial is conducted

Germany, 

References & Publications (13)

Augustin M, Schommers P, Stecher M, Dewald F, Gieselmann L, Gruell H, Horn C, Vanshylla K, Cristanziano VD, Osebold L, Roventa M, Riaz T, Tschernoster N, Altmueller J, Rose L, Salomon S, Priesner V, Luers JC, Albus C, Rosenkranz S, Gathof B, Fatkenheuer G, Hallek M, Klein F, Suarez I, Lehmann C. Post-COVID syndrome in non-hospitalised patients with COVID-19: a longitudinal prospective cohort study. Lancet Reg Health Eur. 2021 Jul;6:100122. doi: 10.1016/j.lanepe.2021.100122. Epub 2021 May 18. — View Citation

Gierhardt M, Pak O, Walmrath D, Seeger W, Grimminger F, Ghofrani HA, Weissmann N, Hecker M, Sommer N. Impairment of hypoxic pulmonary vasoconstriction in acute respiratory distress syndrome. Eur Respir Rev. 2021 Sep 15;30(161):210059. doi: 10.1183/16000617.0059-2021. Print 2021 Sep 30. — View Citation

Kjaergaard S, Rees S, Malczynski J, Nielsen JA, Thorgaard P, Toft E, Andreassen S. Non-invasive estimation of shunt and ventilation-perfusion mismatch. Intensive Care Med. 2003 May;29(5):727-34. doi: 10.1007/s00134-003-1708-0. Epub 2003 Apr 16. — View Citation

Nalbandian A, Sehgal K, Gupta A, Madhavan MV, McGroder C, Stevens JS, Cook JR, Nordvig AS, Shalev D, Sehrawat TS, Ahluwalia N, Bikdeli B, Dietz D, Der-Nigoghossian C, Liyanage-Don N, Rosner GF, Bernstein EJ, Mohan S, Beckley AA, Seres DS, Choueiri TK, Uriel N, Ausiello JC, Accili D, Freedberg DE, Baldwin M, Schwartz A, Brodie D, Garcia CK, Elkind MSV, Connors JM, Bilezikian JP, Landry DW, Wan EY. Post-acute COVID-19 syndrome. Nat Med. 2021 Apr;27(4):601-615. doi: 10.1038/s41591-021-01283-z. Epub 2021 Mar 22. — View Citation

Nuzzi V, Castrichini M, Collini V, Roman-Pognuz E, Di Bella S, Luzzati R, Berlot G, Confalonieri M, Merlo M, Stolfo D, Sinagra G. Impaired Right Ventricular Longitudinal Strain Without Pulmonary Hypertension in Patients Who Have Recovered From COVID-19. Circ Cardiovasc Imaging. 2021 Apr;14(4):e012166. doi: 10.1161/CIRCIMAGING.120.012166. Epub 2021 Apr 8. No abstract available. — View Citation

Reichenberger F, Voswinckel R, Schulz R, Mensch O, Ghofrani HA, Olschewski H, Seeger W. Noninvasive detection of early pulmonary vascular dysfunction in scleroderma. Respir Med. 2009 Nov;103(11):1713-8. doi: 10.1016/j.rmed.2009.05.004. Epub 2009 Jun 3. — View Citation

Rossi R, Coppi F, Monopoli DE, Sgura FA, Arrotti S, Boriani G. Pulmonary arterial hypertension and right ventricular systolic dysfunction in COVID-19 survivors. Cardiol J. 2022;29(1):163-165. doi: 10.5603/CJ.a2021.0159. Epub 2021 Dec 13. No abstract available. — View Citation

Shah W, Hillman T, Playford ED, Hishmeh L. Managing the long term effects of covid-19: summary of NICE, SIGN, and RCGP rapid guideline. BMJ. 2021 Jan 22;372:n136. doi: 10.1136/bmj.n136. No abstract available. Erratum In: BMJ. 2022 Jan 19;376:o126. — View Citation

Sonnweber T, Sahanic S, Pizzini A, Luger A, Schwabl C, Sonnweber B, Kurz K, Koppelstatter S, Haschka D, Petzer V, Boehm A, Aichner M, Tymoszuk P, Lener D, Theurl M, Lorsbach-Kohler A, Tancevski A, Schapfl A, Schaber M, Hilbe R, Nairz M, Puchner B, Huttenberger D, Tschurtschenthaler C, Asshoff M, Peer A, Hartig F, Bellmann R, Joannidis M, Gollmann-Tepekoylu C, Holfeld J, Feuchtner G, Egger A, Hoermann G, Schroll A, Fritsche G, Wildner S, Bellmann-Weiler R, Kirchmair R, Helbok R, Prosch H, Rieder D, Trajanoski Z, Kronenberg F, Woll E, Weiss G, Widmann G, Loffler-Ragg J, Tancevski I. Cardiopulmonary recovery after COVID-19: an observational prospective multicentre trial. Eur Respir J. 2021 Apr 29;57(4):2003481. doi: 10.1183/13993003.03481-2020. Print 2021 Apr. — View Citation

Thomsen LP, Karbing DS, Smith BW, Murley D, Weinreich UM, Kjaergaard S, Toft E, Thorgaard P, Andreassen S, Rees SE. Clinical refinement of the automatic lung parameter estimator (ALPE). J Clin Monit Comput. 2013 Jun;27(3):341-50. doi: 10.1007/s10877-013-9442-9. Epub 2013 Feb 21. — View Citation

Trinkmann F, Benck U, Halder J, Semmelweis A, Saur J, Borggrefe M, Akin I, Kaden JJ. Automated Noninvasive Central Blood Pressure Measurements by Oscillometric Radial Pulse Wave Analysis: Results of the MEASURE-cBP Validation Studies. Am J Hypertens. 2021 Apr 20;34(4):383-393. doi: 10.1093/ajh/hpaa174. — View Citation

Wagner PD. The multiple inert gas elimination technique (MIGET). Intensive Care Med. 2008 Jun;34(6):994-1001. doi: 10.1007/s00134-008-1108-6. Epub 2008 Apr 18. — View Citation

Winkler J, Hagert-Winkler A, Wirtz H, Hoheisel G. [Modern impulse oscillometry in the spectrum of pulmonary function testing methods]. Pneumologie. 2009 Aug;63(8):461-9. doi: 10.1055/s-0029-1214938. Epub 2009 Aug 7. German. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Measurement of gas exchange under different inhaled oxygen concentrations	Non-invasive estimation of ventilation/perfusion (V/Q) mismatch	At the time of presentation (on day 1)
Primary	Spiroergometric capacity- maximal oxygen uptake (VO2max; ml/min/kg)	Determination of exercise capacity by cardiopulmonary exercise testing (CPET)	At the time of presentation (on day 1)
Primary	Echocardiographic right heart parameters - pulmonary arterial systolic pressure (PASP; mmHg)	Echocardiographic determination of right heart parameters under rest and during exercise	At the time of presentation (on day 1)
Primary	Echocardiographic right heart parameters - Tricuspid annular plane systolic excursion (TAPSE; mm)	Echocardiographic determination of right heart parameters under rest and during exercise	At the time of presentation (on day 1)
Primary	Echocardiographic right heart parameters - right ventricular (RV) end-ventricular volume (EDV; ml)	Echocardiographic determination of right heart parameters under rest and during exercise	At the time of presentation (on day 1)
Primary	Echocardiographic right heart - right volume (RV) end-systolic volume (ESV; ml)	Echocardiographic determination of right heart parameters under rest and during exercise	At the time of presentation (on day 1)
Primary	Echocardiographic right heart - right ventricular longitudinal global strain (%)	Echocardiographic determination of right heart parameters under rest and during exercise	At the time of presentation (on day 1)
Primary	Dyspnoea Index	Determination of dyspnea and functional capacity a questionaire measure of shortness of breath for determining exertion levels	At the time of presentation (on day 1)
Primary	Invasive hemodynamics - pulmonary vascular resistance (PVR; WU)	Invasive measurement of pulmonary hemodynamics by right heart catheterization (RHC subgroup)	At the time of presentation (on day 1)
Primary	Invasive hemodynamics - cardiac Index (CI; l/min/m2)	Invasive measurement of pulmonary hemodynamics by right heart catheterization (RHC subgroup)	At the time of presentation (on day 1)
Secondary	Left heart parameters - (E/e' ratio)	Determination of left heart parameters during rest and exercise	At the time of presentation (on day 1)
Secondary	Left heart parameters - left ventricular ejection fraction (%)	Determination of left heart parameters during rest and exercise	At the time of presentation (on day 1)
Secondary	Pulmonary vascular function	Increase of echocardiographically estimated systolic pulmonary arterial pressure during inhalation of hypoxic gas	At the time of presentation (on day 1)
Secondary	Airway Impedance	Determination of airway impedance by oscillometry	At the time of presentation (on day 1)
Secondary	Peripheral blood mononuclear cells	Determination of characteristics of peripheral immune cells by fluorescence activated cell sorter (FACS) and functional assays	At the time of presentation (on day 1)
Secondary	Shunt measurement	Shunt measurement by contrast-enhanced echocardiography (optional)	At the time of presentation (on day 1)
Secondary	Ventilation/Perfusion mismatch	Determination of V/Q mismatch using the gold standard multiple inert gas elimination technique (MIGET) (only in RHC subgroup)	At the time of presentation (on day 1)
Secondary	Static and dynamic lung function parameters - vital capacity (VC; L)	Determination of lung function by body plethysmography at rest	At the time of presentation (on day 1)
Secondary	Static and dynamic lung function parameters - forced expiratory volume in 1 s (FEV1; L)	Determination of lung function by body plethysmography at rest	At the time of presentation (on day 1)
Secondary	Static and dynamic lung function parameters - diffusion capacity (DLCO; %)	Determination of lung function by body plethysmography at rest	At the time of presentation (on day 1)
Secondary	Static and dynamic lung function parameters - diffusion coefficient (DLCO/VA; %)	Determination of lung function by body plethysmography at rest	At the time of presentation (on day 1)