Contrast Enhanced Ultrasound in COVID-19

NCT ID: NCT04640038

Last Updated: 2024-07-30

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

4 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-12-18

Study Completion Date

2021-09-17

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Initial data from COVID-19 patients suggests that one of the primary causes of death is significant endothelial injury leading to blood clotting and impaired multiorgan microvascular perfusion. The current study uses a safe, convenient bedside imaging tool called contrast-enhanced ultrasound (CEUS) to estimate the extent of microvascular perfusion impairment in the heart, kidneys and/or brain of COVID-19 pediatric patients in vivo and assess the significance of imaging findings by correlating to clinical outcomes.

This pilot study will be conducted at one site, The Children's Hospital of Philadelphia. The investigators plan to enroll and evaluate 30 patients.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

The current study uses a safe, convenient bedside imaging tool called contrast-enhanced ultrasound (CEUS) to measure the extent of microvascular perfusion impairment in the heart, kidneys and/or brain of COVID-19 pediatric patients and, as exploratory analysis, to assess the significance of imaging findings by correlating to clinical outcomes.

Sulfur hexafluoride lipid-type A microspheres (LumasonTM, Bracco Inc) is an FDA-approved ultrasound contrast agent. Contrast-enhanced ultrasound scan with a duration of approximately 15 minutes will be performed when a COVID-19 diagnosis has been made (or is highly suspected) according to established clinical procedures. One CEUS will be performed per patient, with up to 2 intravenous injections of the contrast agent. The dosing plan will be weight-adjusted, based on a dose of 0.03 mL/kg (with a maximum dose of 2.4 mL per injection). Organ perfusion will be evaluated in the heart, kidneys, and/or brain. Clinical outcomes during hospital stay will be collected for correlation to CEUS-based measures.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Covid19 Multisystem Inflammatory Syndrome in Children (MIS-C)

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Contrast-enhanced Ultrasonography

Intravenous administration of contrast agent Sulfur hexafluoride lipid-type A microspheres before performing contrast-enhanced ultrasound (CEUS). In pediatric patients, after reconstitution 0.03 mL per kg is administered intravenously. The weight-based dose of 0.03 mL per kg will be repeated one time during a single examination. Following each injection, an intravenous flush of 0.9% Sodium Chloride is injected. The study duration per subject will be approximately 15 minutes including the time to prepare the contrast agent and perform the CEUS, as well as the 60 minute monitoring period after the first and second injection (if there are two injections of contrast) of the contrast agent.

Group Type EXPERIMENTAL

Sulfur hexafluoride lipid-type A microspheres

Intervention Type DRUG

Injection of Sulfur hexafluoride lipid-type A microspheres (Lumason) contrast agent will be performed via the existing peripheral intravenous line using the FDA-recommended dose of 0.03 mg/kg. Two bolus injections will be performed to evaluate for dynamic bowel perfusion and several 2-minute cine clips as well as static images will be acquired during the exam.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Sulfur hexafluoride lipid-type A microspheres

Injection of Sulfur hexafluoride lipid-type A microspheres (Lumason) contrast agent will be performed via the existing peripheral intravenous line using the FDA-recommended dose of 0.03 mg/kg. Two bolus injections will be performed to evaluate for dynamic bowel perfusion and several 2-minute cine clips as well as static images will be acquired during the exam.

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Patient (male/female) hospitalized at the Children's Hospital of Philadelphia (CHOP).
2. Patient 17 years of age or younger.
3. Diagnosis of COVID-19 or high clinical suspicion for COVID-19 despite negative tests (according to the definition of probable case by the European Centre for Disease Prevention and Control).
4. Patients have evidence of cardiovascular compromise, myocardial injury, acute kidney injury and/or new-onset neurological symptoms.
5. Parental/guardian permission (informed consent)

Exclusion Criteria

1\. Medical history of Lumason hypersensitivity
Minimum Eligible Age

1 Minute

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Children's Hospital of Philadelphia

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Misun Hwang, MD

Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

Belhadjer Z, Meot M, Bajolle F, Khraiche D, Legendre A, Abakka S, Auriau J, Grimaud M, Oualha M, Beghetti M, Wacker J, Ovaert C, Hascoet S, Selegny M, Malekzadeh-Milani S, Maltret A, Bosser G, Giroux N, Bonnemains L, Bordet J, Di Filippo S, Mauran P, Falcon-Eicher S, Thambo JB, Lefort B, Moceri P, Houyel L, Renolleau S, Bonnet D. Acute Heart Failure in Multisystem Inflammatory Syndrome in Children in the Context of Global SARS-CoV-2 Pandemic. Circulation. 2020 Aug 4;142(5):429-436. doi: 10.1161/CIRCULATIONAHA.120.048360. Epub 2020 May 17.

Reference Type BACKGROUND
PMID: 32418446 (View on PubMed)

Abdel-Mannan O, Eyre M, Lobel U, Bamford A, Eltze C, Hameed B, Hemingway C, Hacohen Y. Neurologic and Radiographic Findings Associated With COVID-19 Infection in Children. JAMA Neurol. 2020 Nov 1;77(11):1440-1445. doi: 10.1001/jamaneurol.2020.2687.

Reference Type BACKGROUND
PMID: 32609336 (View on PubMed)

Ellul MA, Benjamin L, Singh B, Lant S, Michael BD, Easton A, Kneen R, Defres S, Sejvar J, Solomon T. Neurological associations of COVID-19. Lancet Neurol. 2020 Sep;19(9):767-783. doi: 10.1016/S1474-4422(20)30221-0. Epub 2020 Jul 2.

Reference Type BACKGROUND
PMID: 32622375 (View on PubMed)

Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ. 2020 Mar 31;368:m1295. doi: 10.1136/bmj.m1295. No abstract available.

Reference Type BACKGROUND
PMID: 32234718 (View on PubMed)

Chen L, Li X, Chen M, Feng Y, Xiong C. The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2. Cardiovasc Res. 2020 May 1;116(6):1097-1100. doi: 10.1093/cvr/cvaa078.

Reference Type BACKGROUND
PMID: 32227090 (View on PubMed)

Yao XH, Li TY, He ZC, Ping YF, Liu HW, Yu SC, Mou HM, Wang LH, Zhang HR, Fu WJ, Luo T, Liu F, Guo QN, Chen C, Xiao HL, Guo HT, Lin S, Xiang DF, Shi Y, Pan GQ, Li QR, Huang X, Cui Y, Liu XZ, Tang W, Pan PF, Huang XQ, Ding YQ, Bian XW. [A pathological report of three COVID-19 cases by minimal invasive autopsies]. Zhonghua Bing Li Xue Za Zhi. 2020 May 8;49(5):411-417. doi: 10.3760/cma.j.cn112151-20200312-00193. Chinese.

Reference Type BACKGROUND
PMID: 32172546 (View on PubMed)

Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, Wu Y, Zhang L, Yu Z, Fang M, Yu T, Wang Y, Pan S, Zou X, Yuan S, Shang Y. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020 May;8(5):475-481. doi: 10.1016/S2213-2600(20)30079-5. Epub 2020 Feb 24.

Reference Type BACKGROUND
PMID: 32105632 (View on PubMed)

Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL, Chen HD, Chen J, Luo Y, Guo H, Jiang RD, Liu MQ, Chen Y, Shen XR, Wang X, Zheng XS, Zhao K, Chen QJ, Deng F, Liu LL, Yan B, Zhan FX, Wang YY, Xiao GF, Shi ZL. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020 Mar;579(7798):270-273. doi: 10.1038/s41586-020-2012-7. Epub 2020 Feb 3.

Reference Type BACKGROUND
PMID: 32015507 (View on PubMed)

Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus. J Virol. 2020 Mar 17;94(7):e00127-20. doi: 10.1128/JVI.00127-20. Print 2020 Mar 17.

Reference Type BACKGROUND
PMID: 31996437 (View on PubMed)

Cheng Y, Luo R, Wang K, Zhang M, Wang Z, Dong L, Li J, Yao Y, Ge S, Xu G. Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney Int. 2020 May;97(5):829-838. doi: 10.1016/j.kint.2020.03.005. Epub 2020 Mar 20.

Reference Type BACKGROUND
PMID: 32247631 (View on PubMed)

Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020 Mar 17;323(11):1061-1069. doi: 10.1001/jama.2020.1585.

Reference Type BACKGROUND
PMID: 32031570 (View on PubMed)

Dolhnikoff M, Duarte-Neto AN, de Almeida Monteiro RA, da Silva LFF, de Oliveira EP, Saldiva PHN, Mauad T, Negri EM. Pathological evidence of pulmonary thrombotic phenomena in severe COVID-19. J Thromb Haemost. 2020 Jun;18(6):1517-1519. doi: 10.1111/jth.14844. No abstract available.

Reference Type BACKGROUND
PMID: 32294295 (View on PubMed)

Magro C, Mulvey JJ, Berlin D, Nuovo G, Salvatore S, Harp J, Baxter-Stoltzfus A, Laurence J. Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: A report of five cases. Transl Res. 2020 Jun;220:1-13. doi: 10.1016/j.trsl.2020.04.007. Epub 2020 Apr 15.

Reference Type BACKGROUND
PMID: 32299776 (View on PubMed)

Fox SE, Akmatbekov A, Harbert JL, Li G, Quincy Brown J, Vander Heide RS. Pulmonary and cardiac pathology in African American patients with COVID-19: an autopsy series from New Orleans. Lancet Respir Med. 2020 Jul;8(7):681-686. doi: 10.1016/S2213-2600(20)30243-5. Epub 2020 May 27.

Reference Type BACKGROUND
PMID: 32473124 (View on PubMed)

GOLD E, CARVER DH, HEINEBERG H, ADELSON L, ROBBINS FC. Viral infection. A possible cause of sudden, unexpected death in infants. N Engl J Med. 1961 Jan 12;264:53-60. doi: 10.1056/NEJM196101122640201. No abstract available.

Reference Type BACKGROUND
PMID: 13706404 (View on PubMed)

Ma F, Cang Y, Zhao B, Liu Y, Wang C, Liu B, Wu T, Song Y, Peng A. Contrast-enhanced ultrasound with SonoVue could accurately assess the renal microvascular perfusion in diabetic kidney damage. Nephrol Dial Transplant. 2012 Jul;27(7):2891-8. doi: 10.1093/ndt/gfr789. Epub 2012 Apr 24.

Reference Type BACKGROUND
PMID: 22532616 (View on PubMed)

Cao W, Cui S, Yang L, Wu C, Liu J, Yang F, Liu Y, Bin J, Hou FF. Contrast-Enhanced Ultrasound for Assessing Renal Perfusion Impairment and Predicting Acute Kidney Injury to Chronic Kidney Disease Progression. Antioxid Redox Signal. 2017 Dec 10;27(17):1397-1411. doi: 10.1089/ars.2017.7006. Epub 2017 Aug 22.

Reference Type BACKGROUND
PMID: 28715949 (View on PubMed)

Putz FJ, Erlmeier A, Wiesinger I, Verloh N, Stroszczynski C, Banas B, Jung EM. Contrast-enhanced ultrasound (CEUS) in renal imaging at an interdisciplinary ultrasound centre: Possibilities of dynamic microvascularisation and perfusion. Clin Hemorheol Microcirc. 2017;66(4):293-302. doi: 10.3233/CH-179103.

Reference Type BACKGROUND
PMID: 28527200 (View on PubMed)

Schneider AG, Goodwin MD, Schelleman A, Bailey M, Johnson L, Bellomo R. Contrast-enhanced ultrasound to evaluate changes in renal cortical perfusion around cardiac surgery: a pilot study. Crit Care. 2013 Jul 12;17(4):R138. doi: 10.1186/cc12817.

Reference Type BACKGROUND
PMID: 23849270 (View on PubMed)

Goyal A, Yu FTH, Tenwalde MG, Chen X, Althouse A, Villanueva FS, Pacella JJ. Inertial Cavitation Ultrasound with Microbubbles Improves Reperfusion Efficacy When Combined with Tissue Plasminogen Activator in an In Vitro Model of Microvascular Obstruction. Ultrasound Med Biol. 2017 Jul;43(7):1391-1400. doi: 10.1016/j.ultrasmedbio.2017.02.013. Epub 2017 Apr 7.

Reference Type BACKGROUND
PMID: 28395964 (View on PubMed)

Istvanic F, Yu GZ, Yu FTH, Powers J, Chen X, Pacella JJ. Sonoreperfusion therapy for microvascular obstruction: A step toward clinical translation. Ultrasound Med Biol. 2020 Mar;46(3):712-720. doi: 10.1016/j.ultrasmedbio.2019.11.011. Epub 2020 Jan 7.

Reference Type BACKGROUND
PMID: 31924423 (View on PubMed)

Hwang M. Introduction to contrast-enhanced ultrasound of the brain in neonates and infants: current understanding and future potential. Pediatr Radiol. 2019 Feb;49(2):254-262. doi: 10.1007/s00247-018-4270-1. Epub 2018 Oct 23.

Reference Type BACKGROUND
PMID: 30353273 (View on PubMed)

Hwang M, Riggs BJ, Katz J, Seyfert D, Northington F, Shenandoah R, Burd I, McArthur J, Darge K, Thimm MA, Huisman TAGM. Advanced Pediatric Neurosonography Techniques: Contrast-Enhanced Ultrasonography, Elastography, and Beyond. J Neuroimaging. 2018 Mar;28(2):150-157. doi: 10.1111/jon.12492. Epub 2017 Dec 27.

Reference Type BACKGROUND
PMID: 29280236 (View on PubMed)

Hwang M, De Jong RM Jr, Herman S, Boss R, Riggs B, Tekes-Brady A, Spevak M, Poretti A, Soares BP, Bailey CR, Dunn E, Shin SS, Shrot S, Huisman TAGM. Novel Contrast-Enhanced Ultrasound Evaluation in Neonatal Hypoxic Ischemic Injury: Clinical Application and Future Directions. J Ultrasound Med. 2017 Nov;36(11):2379-2386. doi: 10.1002/jum.14289. Epub 2017 Jun 26.

Reference Type BACKGROUND
PMID: 28649730 (View on PubMed)

Hwang M, Riggs BJ, Saade-Lemus S, Huisman TA. Bedside contrast-enhanced ultrasound diagnosing cessation of cerebral circulation in a neonate: A novel bedside diagnostic tool. Neuroradiol J. 2018 Dec;31(6):578-580. doi: 10.1177/1971400918795866. Epub 2018 Sep 7.

Reference Type BACKGROUND
PMID: 30189812 (View on PubMed)

Hwang M, Sridharan A, Darge K, Riggs B, Sehgal C, Flibotte J, Huisman TAGM. Novel Quantitative Contrast-Enhanced Ultrasound Detection of Hypoxic Ischemic Injury in Neonates and Infants: Pilot Study 1. J Ultrasound Med. 2019 Aug;38(8):2025-2038. doi: 10.1002/jum.14892. Epub 2018 Dec 17.

Reference Type BACKGROUND
PMID: 30560547 (View on PubMed)

Benjamin JL, Dennis R, White S Jr, Munson D, Anupindi SA, Piskunowicz M, Darge K, Gokli A, Hwang M. Improved Diagnostic Sensitivity of Bowel Disease of Prematurity on Contrast-Enhanced Ultrasound. J Ultrasound Med. 2020 May;39(5):1031-1036. doi: 10.1002/jum.15168. Epub 2019 Nov 9.

Reference Type BACKGROUND
PMID: 31705672 (View on PubMed)

Hwang M, Hariri G, Lyshchik A, Hallahan DE, Fleischer AC. Correlation of quantified contrast-enhanced sonography with in vivo tumor response. J Ultrasound Med. 2010 Apr;29(4):597-607. doi: 10.7863/jum.2010.29.4.597.

Reference Type BACKGROUND
PMID: 20375378 (View on PubMed)

Tierradentro-Garcia LO, Sridharan A, Hwang M. Transtemporal brain contrast-enhanced ultrasound in children: preliminary experience in patients without neurological disorders. J Ultrasound. 2023 Mar;26(1):201-210. doi: 10.1007/s40477-022-00713-z. Epub 2022 Aug 27.

Reference Type RESULT
PMID: 36030353 (View on PubMed)

Hwang M, Tierradentro-Garcia LO, Haddad S, Poznick L, Kilbaugh T, Chiotos K. Feasibility of Contrast-Enhanced Ultrasound for Assessing Cardiac and Renal Microvascular Flow in Patients With Multisystem Inflammatory Syndrome in Children. Clin Pediatr (Phila). 2022 Mar;61(3):241-247. doi: 10.1177/00099228211073288. Epub 2022 Jan 26. No abstract available.

Reference Type RESULT
PMID: 35081803 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

Access external resources that provide additional context or updates about the study.

https://doi.org/10.2807/1560-7917.ES.2020.25.6.2002131

Latest updates on COVID-19 from the European Centre for Disease Prevention and Control

https://doi.org/10.1101/2020.03.07.20032524

Diagnosis of Acute Respiratory Syndrome Coronavirus 2 Infection by Detection of Nucleocapsid Protein

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

20-017501

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

CEUS for Blunt Abdominal Trauma in Children
NCT03490929 RECRUITING PHASE4
Effectiveness of Contrast-Enhanced Ultrasound
NCT03473249 ACTIVE_NOT_RECRUITING PHASE4