Clinical trial NCT04369807: Mapping Organ Health Following COVID-19 Disease Due to SARS-CoV-2 Infection
Official title: Mapping Organ Health Following COVID-19 Disease Due to SARS-CoV-2 Infection
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: COVID-19
Keywords: Metabolic Syndrome
Obesity
Fatty Liver Disease
Lead sponsor: Perspectum
Sponsor class: INDUSTRY
First posted: 2020-04-30
Enrollment: 693
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Participants will be recovered or recovering from COVID-19 disease, at least age 18 years and invited to partake in this study. Participants will previously have experienced symptomatic and confirmed COVID-19 disease and will be outpatients able to breath independently without oxygen. Participants will have been discharged back into the community with no respiratory symptoms for at least 7 days. Although subsequent negative testing for infectivity is ideal prior to study entry, participants will be considered non-infectious based on the absence of any fever or severe cough for at least 7 days, as per the advice of the UK Chief Medical Officer.

Brief summary: A prospective, longitudinal, observational cohort study looking at patients following COVID-19 disease using multi-parametric magnetic resonance imaging (MRI) to assess the degree and prevalence of organ injury.

Detailed description: To date, correctly, all of the Government's efforts have been dedicated to providing sufficient hospital space, and the appropriate equipment, for treating the most serious cases of COVID-19. Equally, enormous resource is being dedicated to developing technologies that determine who has the disease, and who has developed antibodies to it.

However, patients recovering from serious disease will also pose a huge, ongoing challenge. Not only are people with co-morbidities including underlying fatty liver disease, metabolic syndrome and diabetes at higher risk for complications with COVID-19; but patients discharged from hospital after severe COVID-19 are reported to have liver and kidney injuries, and impacts on pancreas and spleen. However, the extent of organ health/damage has not been mapped.

This is a prospective, longitudinal, observational cohort study looking at patients recovering from COVID-19 disease using multi-parametric magnetic resonance imaging (MRI) to assess the degree and prevalence of organ injury. This proposed study aims to measure the prevalence of organ volume changes and damage in lungs, heart, kidney, liver, pancreas, spleen as assessed by MRI among those having recovered, or recovering, from the SARS-CoV-2 infection - participants will have a final MRI scan at 12 months. Assessing the severity and sequelae of COVID-19 in patients is crucial to enable global planning for health-care needs. The study includes up to 3 visits for MRI scans and blood tests over a 12 month period. All participants will receive standard-of-care by their healthcare provider/s.

Eligibility criteria: Inclusion Criteria:

* Male or female 18 years of age and older willing and able to give informed consent to participate in the study
* Recent confirmed diagnosis of SARS-CoV-2 RNA via a polymerase chain reaction (PCR) assay (having been discharged 7 or more days from hospital).

Exclusion Criteria:

* Symptoms of active respiratory viral infection:

  * high temperature (over 37.8C/100.04F)
  * cough (consistent for over an hour; 3 or more episodes in 24 hours)
* The participant may not enter the study with any known contraindication to magnetic resonance imaging (including but not limited to pregnancy, a pacemaker or other metallic unfixed implanted device, metallic fragments, extensive tattoos, severe claustrophobia).
* Any other cause, including a significant underlying disease or disorder which, in the opinion of the investigator, may put the participant at risk by participating in the study or limit the participant's ability to participate.

Primary outcomes:
measure: Characterise prevalence and severity of organ volume change and damage (heart, kidneys and liver)
timeFrame: 12 Months
Secondary outcomes:
measure: Characterise prevalence and severity of organ volume change and damage (lung, pancreas and spleen)
timeFrame: 12 Months
measure: Change from Baseline in liver-specific biomarkers: volume, iron corrected T1(cT1), fat content and T2star
timeFrame: 6 Months
measure: Change from Baseline in organ-specific biomarkers characterising organ volume change in the heart and spleen along with organ volume and damage in the kidney, liver and pancreas assessed by volume, iron corrected T1 (cT1) and fat infiltration
timeFrame: 12 Months
measure: Change in patient reported outcome measured by the Dyspnea-12 questionnaire
timeFrame: 12 Months
measure: Change in patient reported outcome measured by the Saint George's Respiratory questionnaire (SGRQ)
timeFrame: 12 Months
measure: Change in patient reported outcome measured by the EQ-5D-5L questionnaire
timeFrame: 12 Months
measure: Degree of change in liver MR-derived biomarkers
timeFrame: 12 Months
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Mayo Clinic Healthcare
city: Oxford
country: United Kingdom
facility: Gemini
Study officials:
affiliation: Honorary Consultant Physician, Oxford University NHS Foundation Trust
name: Rajarshi Banerjee, MSc, DPhil
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bachtiar V, Kelly MD, Wilman HR, Jacobs J, Newbould R, Kelly CJ, Gyngell ML, Groves KE, McKay A, Herlihy AH, Fernandes CC, Halberstadt M, Maguire M, Jayaratne N, Linden S, Neubauer S, Banerjee R. Repeatability and reproducibility of multiparametric magnetic resonance imaging of the liver. PLoS One. 2019 Apr 10;14(4):e0214921. doi: 10.1371/journal.pone.0214921. eCollection 2019.
citation: Banerjee R, Pavlides M, Tunnicliffe EM, Piechnik SK, Sarania N, Philips R, Collier JD, Booth JC, Schneider JE, Wang LM, Delaney DW, Fleming KA, Robson MD, Barnes E, Neubauer S. Multiparametric magnetic resonance for the non-invasive diagnosis of liver disease. J Hepatol. 2014 Jan;60(1):69-77. doi: 10.1016/j.jhep.2013.09.002. Epub 2013 Sep 12.
citation: Bycroft C, Freeman C, Petkova D, Band G, Elliott LT, Sharp K, Motyer A, Vukcevic D, Delaneau O, O'Connell J, Cortes A, Welsh S, Young A, Effingham M, McVean G, Leslie S, Allen N, Donnelly P, Marchini J. The UK Biobank resource with deep phenotyping and genomic data. Nature. 2018 Oct;562(7726):203-209. doi: 10.1038/s41586-018-0579-z. Epub 2018 Oct 10.
citation: Chen T, Wu D, Chen H, Yan W, Yang D, Chen G, Ma K, Xu D, Yu H, Wang H, Wang T, Guo W, Chen J, Ding C, Zhang X, Huang J, Han M, Li S, Luo X, Zhao J, Ning Q. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ. 2020 Mar 26;368:m1091. doi: 10.1136/bmj.m1091.
citation: 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.
citation: Ding Y, He L, Zhang Q, Huang Z, Che X, Hou J, Wang H, Shen H, Qiu L, Li Z, Geng J, Cai J, Han H, Li X, Kang W, Weng D, Liang P, Jiang S. Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways. J Pathol. 2004 Jun;203(2):622-30. doi: 10.1002/path.1560.
citation: Driggin E, Madhavan MV, Bikdeli B, Chuich T, Laracy J, Biondi-Zoccai G, Brown TS, Der Nigoghossian C, Zidar DA, Haythe J, Brodie D, Beckman JA, Kirtane AJ, Stone GW, Krumholz HM, Parikh SA. Cardiovascular Considerations for Patients, Health Care Workers, and Health Systems During the COVID-19 Pandemic. J Am Coll Cardiol. 2020 May 12;75(18):2352-2371. doi: 10.1016/j.jacc.2020.03.031. Epub 2020 Mar 19.
citation: Grasselli G, Pesenti A, Cecconi M. Critical Care Utilization for the COVID-19 Outbreak in Lombardy, Italy: Early Experience and Forecast During an Emergency Response. JAMA. 2020 Apr 28;323(16):1545-1546. doi: 10.1001/jama.2020.4031. No abstract available.
citation: Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, Du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS; China Medical Treatment Expert Group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Apr 30;382(18):1708-1720. doi: 10.1056/NEJMoa2002032. Epub 2020 Feb 28.
citation: Gurwitz D. Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics. Drug Dev Res. 2020 Aug;81(5):537-540. doi: 10.1002/ddr.21656. Epub 2020 Mar 4.
citation: Harrison SA, Bashir MR, Guy CD, Zhou R, Moylan CA, Frias JP, Alkhouri N, Bansal MB, Baum S, Neuschwander-Tetri BA, Taub R, Moussa SE. Resmetirom (MGL-3196) for the treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet. 2019 Nov 30;394(10213):2012-2024. doi: 10.1016/S0140-6736(19)32517-6. Epub 2019 Nov 11.
citation: Harrison SA, Rossi SJ, Paredes AH, Trotter JF, Bashir MR, Guy CD, Banerjee R, Jaros MJ, Owers S, Baxter BA, Ling L, DePaoli AM. NGM282 Improves Liver Fibrosis and Histology in 12 Weeks in Patients With Nonalcoholic Steatohepatitis. Hepatology. 2020 Apr;71(4):1198-1212. doi: 10.1002/hep.30590. Epub 2019 Apr 10.
citation: Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24.
citation: Pavlides M, Banerjee R, Sellwood J, Kelly CJ, Robson MD, Booth JC, Collier J, Neubauer S, Barnes E. Multiparametric magnetic resonance imaging predicts clinical outcomes in patients with chronic liver disease. J Hepatol. 2016 Feb;64(2):308-315. doi: 10.1016/j.jhep.2015.10.009. Epub 2015 Nov 10.
citation: Pavlides M, Banerjee R, Tunnicliffe EM, Kelly C, Collier J, Wang LM, Fleming KA, Cobbold JF, Robson MD, Neubauer S, Barnes E. Multiparametric magnetic resonance imaging for the assessment of non-alcoholic fatty liver disease severity. Liver Int. 2017 Jul;37(7):1065-1073. doi: 10.1111/liv.13284. Epub 2017 May 30.
citation: Verity R, Okell LC, Dorigatti I, Winskill P, Whittaker C, Imai N, Cuomo-Dannenburg G, Thompson H, Walker PGT, Fu H, Dighe A, Griffin JT, Baguelin M, Bhatia S, Boonyasiri A, Cori A, Cucunuba Z, FitzJohn R, Gaythorpe K, Green W, Hamlet A, Hinsley W, Laydon D, Nedjati-Gilani G, Riley S, van Elsland S, Volz E, Wang H, Wang Y, Xi X, Donnelly CA, Ghani AC, Ferguson NM. Estimates of the severity of coronavirus disease 2019: a model-based analysis. Lancet Infect Dis. 2020 Jun;20(6):669-677. doi: 10.1016/S1473-3099(20)30243-7. Epub 2020 Mar 30.
citation: Wang T, Du Z, Zhu F, Cao Z, An Y, Gao Y, Jiang B. Comorbidities and multi-organ injuries in the treatment of COVID-19. Lancet. 2020 Mar 21;395(10228):e52. doi: 10.1016/S0140-6736(20)30558-4. Epub 2020 Mar 11. No abstract available.
citation: Xu L, Liu J, Lu M, Yang D, Zheng X. Liver injury during highly pathogenic human coronavirus infections. Liver Int. 2020 May;40(5):998-1004. doi: 10.1111/liv.14435. Epub 2020 Mar 30.
citation: Zhang C, Shi L, Wang FS. Liver injury in COVID-19: management and challenges. Lancet Gastroenterol Hepatol. 2020 May;5(5):428-430. doi: 10.1016/S2468-1253(20)30057-1. Epub 2020 Mar 4. No abstract available.
citation: Dennis A, Cuthbertson DJ, Wootton D, Crooks M, Gabbay M, Eichert N, Mouchti S, Pansini M, Roca-Fernandez A, Thomaides-Brears H, Kelly M, Robson M, Hishmeh L, Attree E, Heightman M, Banerjee R, Banerjee A. Multi-organ impairment and long COVID: a 1-year prospective, longitudinal cohort study. J R Soc Med. 2023 Mar;116(3):97-112. doi: 10.1177/01410768231154703. Epub 2023 Feb 14.
citation: Roca-Fernandez A, Dennis A, Nicholls R, McGonigle J, Kelly M, Banerjee R, Banerjee A, Sanyal AJ. Hepatic Steatosis, Rather Than Underlying Obesity, Increases the Risk of Infection and Hospitalization for COVID-19. Front Med (Lausanne). 2021 Mar 29;8:636637. doi: 10.3389/fmed.2021.636637. eCollection 2021.
citation: Davis HE, McCorkell L, Vogel JM, Topol EJ. Long COVID: major findings, mechanisms and recommendations. Nat Rev Microbiol. 2023 Mar;21(3):133-146. doi: 10.1038/s41579-022-00846-2. Epub 2023 Jan 13.
citation: Roca-Fernandez A, Wamil M, Telford A, Carapella V, Borlotti A, Monteiro D, Thomaides-Brears H, Kelly M, Dennis A, Banerjee R, Robson M, Brady M, Lip GYH, Bull S, Heightman M, Ntusi N, Banerjee A. Cardiac abnormalities in Long COVID 1-year post-SARS-CoV-2 infection. Open Heart. 2023 Feb;10(1):e002241. doi: 10.1136/openhrt-2022-002241.
citation: Borlotti A, Thomaides-Brears H, Georgiopoulos G, Banerjee R, Robson MD, Fusco DN, Masci PG. The Additive Value of Cardiovascular Magnetic Resonance in Convalescent COVID-19 Patients. Front Cardiovasc Med. 2022 Apr 7;9:854750. doi: 10.3389/fcvm.2022.854750. eCollection 2022.
citation: Dennis A, Wamil M, Alberts J, Oben J, Cuthbertson DJ, Wootton D, Crooks M, Gabbay M, Brady M, Hishmeh L, Attree E, Heightman M, Banerjee R, Banerjee A; COVERSCAN study investigators. Multiorgan impairment in low-risk individuals with post-COVID-19 syndrome: a prospective, community-based study. BMJ Open. 2021 Mar 30;11(3):e048391. doi: 10.1136/bmjopen-2020-048391.