Modulation of Hyperinflammation in COVID-19

NCT04353674 | Completed DMC

• 1 other identifier: 115785
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

Current treatment recommendations are based on very limited evidence and reliant on the deployment of pharmacological strategies of doubtful efficacy, high toxicity, and near universal shortages of supply. On a global scale, there is a desperate need for readily available therapeutic options to safely and cost effectively target the hyper-inflammatory state in ICU patients based on management of severe COVID-19 (evidence of acute respiratory distress syndrome). The study team proposes to use slow low-efficiency daily dialysis to provide an extracorporeal circuit to target this cytokine storm using immunomodulation of neutrophils with a novel leucocyte modulatory device (L-MOD) to generate an anti-inflammatory phenotype, but without depletion of circulating factors.

Conditions

COVID-19; SARS

Keywords

cytokine storm; SLEDD

Outcome Measures

Primary Outcomes (1)

• Efficacy of a L-MOD against controls receiving supportive care in ICU.

  Efficacy will be evaluated by reduction of vasopressor support (converted to norepinephrine dose equivalents) compared to control group.

  Through dialysis, on average of 12 hours, two days in a row

Secondary Outcomes (9)

• Mortality

  From date of randomization until the date of death from any cause, whichever came first, assessed up to 2 months

• Hospital Discharge

  From date of randomization until the date of hospital discharge or death from any cause, whichever came first, assessed up to 2 months

• Leukocyte Monitoring

  Through dialysis, on average of 12 hours, two days in a row and again on day 5 in the ICU

• Sequential Organ Failure Assessment (SOFA) Score

  From date of randomization until the date of ICU discharge or death from any cause, whichever came first, assessed up to 1 months

• Intubation length

  From date of randomization until the date of ICU discharge up to 2 months

Study Arms (2)

Control

SHAM COMPARATOR

Patients diagnosed with severe COVID-19: Those admitted to the intensive care unit with evidence of severe respiratory distress syndrome will undergo standard of care

Device: Control group

SLEDD with a L-MOD

ACTIVE COMPARATOR

Patients diagnosed with severe COVID-19: Those admitted to the intensive care unit with evidence of severe respiratory distress syndrome will undergo slow low efficiency daily dialysis for approximately 12 hours, 2 days in a row with a leukocyte modulatory device.

Device: SLEDD with a L-MOD

Interventions

Control group DEVICE

Patients randomized into this group will receive standard of care for COVID-19 infection

Control

SLEDD with a L-MOD DEVICE

Patients randomized to this group will undergo slow low efficiency daily dialysis for approximately 12 hours, 2 days in a row with a leukocyte modulatory device.

SLEDD with a L-MOD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age greater than or equal to 18 years
• High clinical suspicion of COVID-19 from the opinion of both infectious disease specialist (s) and the ICU team
• Evidence of acute respiratory distress syndrome requiring admission to the Critical Care Trauma Centre Medical Surgical ICU, or the Cardiac Surgical Recovery Unit
• Vasopressor support

You may not qualify if:

• Pregnant
• Unconfirmed COVID-19
• Chronic immune depression
• Contra-indications to regional citrate anticoagulation

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead

Study Sites (2)

University Hospital

London, Ontario, N6A 5A5, Canada

Location

Victoria Hospital - Critical Care Trauma Centre

London, Ontario, N6C 2V4, Canada

Location

Related Publications (17)

• Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020 Apr 7;323(13):1239-1242. doi: 10.1001/jama.2020.2648. No abstract available.

  PMID: 32091533 RESULT

• Deng Y, Liu W, Liu K, Fang YY, Shang J, Zhou L, Wang K, Leng F, Wei S, Chen L, Liu HG. Clinical characteristics of fatal and recovered cases of coronavirus disease 2019 in Wuhan, China: a retrospective study. Chin Med J (Engl). 2020 Jun 5;133(11):1261-1267. doi: 10.1097/CM9.0000000000000824.

  PMID: 32209890 RESULT

• Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, Huang H, Zhang L, Zhou X, Du C, Zhang Y, Song J, Wang S, Chao Y, Yang Z, Xu J, Zhou X, Chen D, Xiong W, Xu L, Zhou F, Jiang J, Bai C, Zheng J, Song Y. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med. 2020 Jul 1;180(7):934-943. doi: 10.1001/jamainternmed.2020.0994.

  PMID: 32167524 RESULT

• Rosenbaum L. Facing Covid-19 in Italy - Ethics, Logistics, and Therapeutics on the Epidemic's Front Line. N Engl J Med. 2020 May 14;382(20):1873-1875. doi: 10.1056/NEJMp2005492. Epub 2020 Mar 18. No abstract available.

  PMID: 32187459 RESULT

• Perlman S, Dandekar AA. Immunopathogenesis of coronavirus infections: implications for SARS. Nat Rev Immunol. 2005 Dec;5(12):917-27. doi: 10.1038/nri1732.

  PMID: 16322745 RESULT

• Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ; HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020 Mar 28;395(10229):1033-1034. doi: 10.1016/S0140-6736(20)30628-0. Epub 2020 Mar 16. No abstract available.

  PMID: 32192578 RESULT

• Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020 May;46(5):846-848. doi: 10.1007/s00134-020-05991-x. Epub 2020 Mar 3. No abstract available.

  PMID: 32125452 RESULT

• Perlman S, Netland J. Coronaviruses post-SARS: update on replication and pathogenesis. Nat Rev Microbiol. 2009 Jun;7(6):439-50. doi: 10.1038/nrmicro2147.

  PMID: 19430490 RESULT

• Jiang Y, Xu J, Zhou C, Wu Z, Zhong S, Liu J, Luo W, Chen T, Qin Q, Deng P. Characterization of cytokine/chemokine profiles of severe acute respiratory syndrome. Am J Respir Crit Care Med. 2005 Apr 15;171(8):850-7. doi: 10.1164/rccm.200407-857OC. Epub 2005 Jan 18.

  PMID: 15657466 RESULT

• Cheung CY, Poon LL, Ng IH, Luk W, Sia SF, Wu MH, Chan KH, Yuen KY, Gordon S, Guan Y, Peiris JS. Cytokine responses in severe acute respiratory syndrome coronavirus-infected macrophages in vitro: possible relevance to pathogenesis. J Virol. 2005 Jun;79(12):7819-26. doi: 10.1128/JVI.79.12.7819-7826.2005.

  PMID: 15919935 RESULT

• He L, Ding Y, Zhang Q, Che X, He Y, Shen H, Wang H, Li Z, Zhao L, Geng J, Deng Y, Yang L, Li J, Cai J, Qiu L, Wen K, Xu X, Jiang S. Expression of elevated levels of pro-inflammatory cytokines in SARS-CoV-infected ACE2+ cells in SARS patients: relation to the acute lung injury and pathogenesis of SARS. J Pathol. 2006 Nov;210(3):288-97. doi: 10.1002/path.2067.

  PMID: 17031779 RESULT

• Nicholls JM, Poon LL, Lee KC, Ng WF, Lai ST, Leung CY, Chu CM, Hui PK, Mak KL, Lim W, Yan KW, Chan KH, Tsang NC, Guan Y, Yuen KY, Peiris JS. Lung pathology of fatal severe acute respiratory syndrome. Lancet. 2003 May 24;361(9371):1773-8. doi: 10.1016/s0140-6736(03)13413-7.

  PMID: 12781536 RESULT

• Alhazzani W, Moller MH, Arabi YM, Loeb M, Gong MN, Fan E, Oczkowski S, Levy MM, Derde L, Dzierba A, Du B, Aboodi M, Wunsch H, Cecconi M, Koh Y, Chertow DS, Maitland K, Alshamsi F, Belley-Cote E, Greco M, Laundy M, Morgan JS, Kesecioglu J, McGeer A, Mermel L, Mammen MJ, Alexander PE, Arrington A, Centofanti JE, Citerio G, Baw B, Memish ZA, Hammond N, Hayden FG, Evans L, Rhodes A. Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19). Crit Care Med. 2020 Jun;48(6):e440-e469. doi: 10.1097/CCM.0000000000004363.

  PMID: 32224769 RESULT

• Ding F, Song JH, Jung JY, Lou L, Wang M, Charles L, Westover A, Smith PL, Pino CJ, Buffington DA, Humes HD. A biomimetic membrane device that modulates the excessive inflammatory response to sepsis. PLoS One. 2011 Apr 14;6(4):e18584. doi: 10.1371/journal.pone.0018584.

  PMID: 21533222 RESULT

• Ding F, Yevzlin AS, Xu ZY, Zhou Y, Xie QH, Liu JF, Zheng Y, DaSilva JR, Humes HD. The effects of a novel therapeutic device on acute kidney injury outcomes in the intensive care unit: a pilot study. ASAIO J. 2011 Sep-Oct;57(5):426-32. doi: 10.1097/MAT.0b013e31820a1494.

  PMID: 21317636 RESULT

• Humes HD, Sobota JT, Ding F, Song JH; RAD Investigator Group. A selective cytopheretic inhibitory device to treat the immunological dysregulation of acute and chronic renal failure. Blood Purif. 2010;29(2):183-90. doi: 10.1159/000245645. Epub 2010 Jan 8.

  PMID: 20093825 RESULT

• Tumlin JA, Galphin CM, Tolwani AJ, Chan MR, Vijayan A, Finkel K, Szamosfalvi B, Dev D, DaSilva JR, Astor BC, Yevzlin AS, Humes HD; SCD Investigator Group. A Multi-Center, Randomized, Controlled, Pivotal Study to Assess the Safety and Efficacy of a Selective Cytopheretic Device in Patients with Acute Kidney Injury. PLoS One. 2015 Aug 5;10(8):e0132482. doi: 10.1371/journal.pone.0132482. eCollection 2015.

  PMID: 26244978 RESULT

MeSH Terms

Conditions

COVID-19; Cytokine Release Syndrome

Interventions

Control Groups

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Study Officials

• Christopher W McIntyre, MD

  Western University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Single centre, prospective, randomized controlled pilot study with approximately 40 patients to be included: 20 in the control group and 20 patients in the L-MOD-SLEDD group.

Study Record Dates

• First Submitted: April 7, 2020
• First Posted: April 20, 2020
• Study Start: April 28, 2020
• Primary Completion: December 30, 2023
• Study Completion: March 15, 2024
• Last Updated: March 29, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2)