Pulmonary Optical Coherence Tomography in COVID-19 Patients
NCT ID: NCT04410549
Last Updated: 2021-10-27
Study Results
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Basic Information
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COMPLETED
NA
13 participants
INTERVENTIONAL
2020-06-01
2021-09-30
Brief Summary
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Detailed Description
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Optical coherence tomography:The optical coherence tomography (OCT) is a near-infrared light source-based imaging technique with a resolution of 10-20 um. It acquires longitudinal sequences of cross-sectional images (100 frames/s) in a blood-free environment, resulting in sharp border definition between lumen and vessel wall. It is routinely used in percutaneous coronary intervention (PCI) to better characterize vessel anatomy, as well as ascertainment of full stent deployment and expansion. Moreover, OCT has been shown to have a good correlation with histology even in the evaluation of pulmonary artery morphology, particularly in the evaluation of pulmonary arterial wall thickness. Furthermore, OCT has been used to better characterized distal Type Chronic Thromboembolic Pulmonary Hypertension, and to guide its treatment with percutaneous transluminal pulmonary angioplasty. Hong et al evaluated with OCT three patients who were highly suspected for peripheral pulmonary arteries thrombi but had negative CT scan for pulmonary embolism. Thrombi were found in most of imaged vessels in these patients. Red and white thrombi can be differentiated, according to features of the thrombus on OCT images. After anticoagulation treatment, these patients' symptoms and hypoxemia improved. Repeated OCT imaging showed that most thrombi disappeared or became smaller. OCT was also used in evaluation of pulmonary arterial vasculopathy in Systemic Sclerosis, showing an unexpected evidence of pulmonary artery thrombus formation in 19% of systemic-sclerosis patients with pulmonary arterial hypertension.
There are sufficient data showing OCT to be a useful tool to identify intravascular thrombi in patients with chronic thromboembolic pulmonary hypertension, together with an increase in vessel wall thickness in most patients with pulmonary hypertension.
Aim of the study:To evaluate by intravascular OCT study the presence of microvascular pulmonary thrombosis in patients with COVID-19, high D-dimer levels and contrast CT scan negative for pulmonary thrombosis. Investigators will also evaluate the extension of microvascular pulmonary thrombosis in patients with contrast CT scan positive for pulmonary embolism in areas where contrast CT scan was negative.
Inclusion Criteria (part A): 1) Severe pulmonary coronarvirus disease 19 (COVID 19) with suspect for MicroCLOTS (microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome) AND 2) Contrast CT scan negative for pulmonary thrombosis AND 3) D-Dimer \> 10 mcg/mL OR 4) 5 \< D-dimer \< 10 mcg/mL and either C Reactive Protein (CRP) \> 100 mg/dL or IL-6 \> 6 pg/mL or ferritin \> 900 ng/L; (part B): 1) Severe pulmonary coronarvirus disease 19 (COVID 19) with suspect for MicroCLOTS (microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome) AND 2) Contrast CT scan positive for pulmonary thrombosis
Exclusion Criteria: 1) Age \< 18 2) Pregnancy or breastfeeding 3) Known allergy to iodinated contrast dye 4) Hemodynamic instability 5) Glomerular Filtration rate \< 30 ml/min 6) Active bleeding or absolute contraindication to anticoagulant therapy
OCT procedure: Femoral vein echo-guided puncture; 6 Fr 11 cm sheath insertion; Unfractionated heparin administration (70 - 100 U/kg) to achieve an activated clotting time (ACT) between 250 and 300 seconds; Pulmonary artery cannulation with 5 Fr Multipurpose (MP) catheter (Cordis, Dublin, Ohio) and Storq wire (Cordis); Pulmonary artery pressure measurement; Selective pulmonary artery cannulation and angiography (The choice of the pulmonary arteries to be cannulated will be driven by "ground glass" area at CT scan); 5Fr MP catheter will be changed for 6Fr MP guiding catheter over the Storq wire; Storq wire removal and 0.014" Balance wire distally advanced; OCT images acquisition (In order to remove all the blood, as well as to obtain clear images, iodinated contrast is infused at a flow rate of 5 mL/s over 4 s, at 400 psi of pressure (Acist, Eden Prairie, Minnesota). Automatic pullback at 20 mm/s); If needed, blood samples can be taken through Recover catheter (Hexacath, Rueil-Malmaison, France).
The same procedure will be performed: on "healthy" (without ground glass appearance at CT scan) area in the same lung and on contralateral lung, both in "ground glass" and "healthy" areas according to CT scan.
PRIMARY ENDPOINT: 1) Overall safety of OCT procedure in COVID-19 pneumonia patients 2) Presence of microvascular pulmonary thrombosis at OCT assessment in COVID-19 patients, both in "ground glass" and "healthy" ventilated areas.
SECONDARY ENDPOINT: 1) Pulmonary artery vessel anatomy characterization in COVID-19 patients 2) Correlations with single trans-thoracic echocardiography (TTE) pulmonary hypertension (PH, estimated systolic pulmonary artery pressure \> 35 mmHg) and right ventricular disfunction (RVD: tricuspid annular plane systolic excursion \< 17 mm or Doppler tissue imaging S wave \< 9.5 cm/sec) 3) Dynamic correlations with standard inflammatory, coagulation and tissue damage biomarkers: CRP, ferritin, D-dimer, NT-proBNPO, troponins, LDH)
Study design, sample size, statistical analysis: The study is an open label, prospective, interventional clinical study of the safety, tolerability and potential diagnostic value of optical coherence tomography for microvascular lung vessels obstructive thromboinflammatory syndrome assessment in patients with COVID-19 pneumonia.
This is an exploratory study and will be conducted in 10 patients with mild-to-severe ARDS. The sample size calculation was designed for safety assessment based on a reference population of last 100 patients who underwent OCT at our Institution for coronary Artery Disease (CAD) in which a rate of SAEs lower than 1% have been recorded (personal communication)
Primary endpoint: As for safety analysis, the number of ADR (expected/unexpected) and SAEs (expected/unexpected and/or related/not related) and the percentage of subjects experiencing ADR and SAEs in the study will be summarized by severity and within body system involved. Narratives will also be presented.
Secondary endpoints: Continuous variables will be summarized with indices of location (i.e. mean or median) and dispersion (i.e. standard deviation or interquartile range), as appropriate. All relevant estimates will be reported with the corresponding 95% Confidence Intervals (CI).
The time to event endpoints will be described using the Kaplan-Meier approach and estimates at pre-defined time points will be obtained along with 95%Cis. Patients will be censored at study closure, withdrawn of consent or loss to follow-up.
Subgroup analyses and regression models (i.e. logistic model on proportions and Cox model on time to event outcomes) will be performed considering age, sex, biological features.
Withdrawal and Premature Termination or Suspension of Study Investigators may terminate a study subject's participation in the study if: any clinical AE, or other medical condition or situation occurs such that continued participation in the study would not be in the best interest of the subject, the subject meets an exclusion criterion, either newly developed or not previously recognized (except those caused by ARDS and SARS-CoV-2 infection), that precludes further study participation; this study may be suspended or prematurely terminated if there is sufficient reasonable cause. Written notification, documenting the reason for study suspension or termination, will be provided.
Fundings: not appropriate. The procedure will be charged to SSN as a diagnostic procedure applied to patients clinically suspected of microCLOTS in COVID-19 pneumonia.
Conditions
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Keywords
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Study Design
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NA
SINGLE_GROUP
DIAGNOSTIC
NONE
Study Groups
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COVID-19 patient with pulmonary thrombosis
* patients with COVID-19, high D-dimer levels and contrast CT scan negative for pulmonary thrombosis
* patients with contrast CT scan positive for pulmonary embolism in areas where contrast CT scan was negative.
Optical Coherence Tomography (OCT)
To perform OCT in pulmonary artery of patient with COVID-19
Interventions
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Optical Coherence Tomography (OCT)
To perform OCT in pulmonary artery of patient with COVID-19
Eligibility Criteria
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Inclusion Criteria
* Severe pulmonary coronarvirus disease 19 (COVID 19) with suspect for MicroCLOTS (microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome) AND
* Contrast CT scan negative for pulmonary thrombosis AND
* D-Dimer \> 10 mcg/mL OR
* 5 \< D-dimer \< 10 mcg/mL and either C Reactive Protein (CRP) \> 100 mg/dL or IL-6 \> 6 pg/mL or ferritin \> 900 ng/L
(part B)
* Severe pulmonary coronarvirus disease 19 (COVID 19) with suspect for MicroCLOTS (microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome) AND
* Contrast CT scan positive for pulmonary thrombosis
Exclusion Criteria
* Pregnancy or breastfeeding
* Known allergy to iodinated contrast dye
* Hemodynamic instability
* Glomerular Filtration rate \< 30 ml/min
* Active bleeding or absolute contraindication to anticoagulant therapy
18 Years
ALL
No
Sponsors
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IRCCS San Raffaele
OTHER
Responsible Party
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Matteo Montorfano
Interventional Cardiology Unit Director
Locations
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Incor - Heart Institute - University of Sao Paulo
São Paulo, , Brazil
IRCCS San Raffaele
Milan, , Italy
Countries
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References
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Ciceri F, Beretta L, Scandroglio AM, Colombo S, Landoni G, Ruggeri A, Peccatori J, D'Angelo A, De Cobelli F, Rovere-Querini P, Tresoldi M, Dagna L, Zangrillo A. Microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome (MicroCLOTS): an atypical acute respiratory distress syndrome working hypothesis. Crit Care Resusc. 2020 Apr 15;22(2):95-97. doi: 10.51893/2020.2.pov2. Online ahead of print.
Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020 Apr;18(4):844-847. doi: 10.1111/jth.14768. Epub 2020 Mar 13.
Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062. doi: 10.1016/S0140-6736(20)30566-3. Epub 2020 Mar 11.
Tearney GJ, Regar E, Akasaka T, Adriaenssens T, Barlis P, Bezerra HG, Bouma B, Bruining N, Cho JM, Chowdhary S, Costa MA, de Silva R, Dijkstra J, Di Mario C, Dudek D, Falk E, Feldman MD, Fitzgerald P, Garcia-Garcia HM, Gonzalo N, Granada JF, Guagliumi G, Holm NR, Honda Y, Ikeno F, Kawasaki M, Kochman J, Koltowski L, Kubo T, Kume T, Kyono H, Lam CC, Lamouche G, Lee DP, Leon MB, Maehara A, Manfrini O, Mintz GS, Mizuno K, Morel MA, Nadkarni S, Okura H, Otake H, Pietrasik A, Prati F, Raber L, Radu MD, Rieber J, Riga M, Rollins A, Rosenberg M, Sirbu V, Serruys PW, Shimada K, Shinke T, Shite J, Siegel E, Sonoda S, Suter M, Takarada S, Tanaka A, Terashima M, Thim T, Uemura S, Ughi GJ, van Beusekom HM, van der Steen AF, van Es GA, van Soest G, Virmani R, Waxman S, Weissman NJ, Weisz G; International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT). Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation. J Am Coll Cardiol. 2012 Mar 20;59(12):1058-72. doi: 10.1016/j.jacc.2011.09.079.
Wijns W, Shite J, Jones MR, Lee SW, Price MJ, Fabbiocchi F, Barbato E, Akasaka T, Bezerra H, Holmes D. Optical coherence tomography imaging during percutaneous coronary intervention impacts physician decision-making: ILUMIEN I study. Eur Heart J. 2015 Dec 14;36(47):3346-55. doi: 10.1093/eurheartj/ehv367. Epub 2015 Aug 4.
Li N, Zhang S, Hou J, Jang IK, Yu B. Assessment of pulmonary artery morphology by optical coherence tomography. Heart Lung Circ. 2012 Dec;21(12):778-81. doi: 10.1016/j.hlc.2012.07.014. Epub 2012 Aug 10.
Hong C, Wang W, Zhong NS, Zeng GQ, Wu H. Using optical coherence tomography to detect peripheral pulmonary thrombi. Chin Med J (Engl). 2012 Sep;125(17):3171-4.
Schwaiger JP, Loder CD, Dobarro D, Kaier T, Reddecliffe S, Schreiber BE, Handler C, Denton CP, Coghlan JG. Optical coherence tomography evaluation of pulmonary arterial vasculopathy in Systemic Sclerosis. Sci Rep. 2017 Feb 24;7:43304. doi: 10.1038/srep43304.
Dai Z, Fukumoto Y, Tatebe S, Sugimura K, Miura Y, Nochioka K, Aoki T, Miyamichi-Yamamoto S, Yaoita N, Satoh K, Shimokawa H. OCT imaging for the management of pulmonary hypertension. JACC Cardiovasc Imaging. 2014 Aug;7(8):843-5. doi: 10.1016/j.jcmg.2014.01.020. No abstract available.
van der Sijde JN, Karanasos A, van Ditzhuijzen NS, Okamura T, van Geuns RJ, Valgimigli M, Ligthart JM, Witberg KT, Wemelsfelder S, Fam JM, Zhang B, Diletti R, de Jaegere PP, van Mieghem NM, van Soest G, Zijlstra F, van Domburg RT, Regar E. Safety of optical coherence tomography in daily practice: a comparison with intravascular ultrasound. Eur Heart J Cardiovasc Imaging. 2017 Apr 1;18(4):467-474. doi: 10.1093/ehjci/jew037.
Hajjar LA, Ancona MB, Filho RK, Tresoldi M, Caldas JG, Monti G, Carnevale FC, De Cobelli F, Moreira de Assis A, Ciceri F, Landoni G, Dijkstra J, Moroni F, Abizaid AAC, Willemann Ungaretti F, Carvalho Carmona MJ, De Backer D, Pompilio CE, de Britto FS Jr, Campos CM, Zangrillo A, Montorfano M. Microvascular lung vessels obstructive thromboinflammatory syndrome in patients with COVID-19: Insights from lung intravascular optical coherence tomography. Front Med (Lausanne). 2023 Feb 16;10:1050531. doi: 10.3389/fmed.2023.1050531. eCollection 2023.
Provided Documents
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Document Type: Study Protocol
Other Identifiers
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OCT COVID
Identifier Type: -
Identifier Source: org_study_id