Pilot Study on Cytokine Filtration in COVID-19 ARDS

NCT04361526 | Unknown

• 1 other identifier: HCB/2020/0464
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Background: There are no proven therapies for COVID-19 infection. COVID-19 infects the respiratory epithelium of the lower airways, causing widespread damage via cytopathic effects, resulting in severe inflammation and Pneumonitis. High local and circulating levels of cytokines, or cytokine storm, can lead to capillary leak syndrome, progressive lung injury, respiratory failure and acute respiratory distress syndrome (ARDS). Methods: This is a pilot randomized, controlled, uni-center study testing safety and efficacy of cytokine filtration on patients with severe ARDS. Eligible patients will be randomized to 72 hours filtration or no filtration on top of the standard treatment for ARDS. Indications for randomization are patients with moderate or severe ARDS with need of ventilation support (either invasive or non-invasive), with inflammatory markers. The primary outcome will be days on mechanical ventilation (MV) support. Secondary outcomes are 30-day mortality, ICU days, need for extracorporeal membrane oxygenation (ECMO) support, duration of renal replacement therapy (RRT) and catecholamine therapies, hospital length of stay, multi-organ failure. All analysis will be done according to the intention to treat principle.

Conditions

Coronavirus Infection; Acute Respiratory Distress Syndrome; COVID

Keywords

COVID; ARDS; Coronavirus

Outcome Measures

Primary Outcomes (1)

• Mechanical ventilation-free days

  Number of ventilator-free days (VFDs) at day 28 (defined as days being alive and free from mechanical ventilation at day 28 after enrollment. For patients ventilated 28 days or longer and for ventilated subjects who die, VFD is 0

  up to 28days

Secondary Outcomes (6)

• 30-day mortality

  up to 30 days

• length of ICU stay (days)

  up to 30 days

• length of hospital stay

  up to 30 days

• Duration of renal replacement and cathecolamines therapies

  up to 30 days

• Need for extracorporeal membrane oxygenation (ECMO) support

  up to 30 days

Study Arms (2)

Control

NO INTERVENTION

standard intensive care alone

Cytokine Adsorption

EXPERIMENTAL

cytokine adsorption plus standard intensive care

Device: Cytokine Adsorption

Interventions

Cytokine Adsorption DEVICE

Cytokine adsorption will be performed through a venous hemodialysis catheter, preferably jugular or femoral. The filtration system will be established with a cytokine adsorption cartridge in an hemoperfusion system using a blood flow rate of 150 - 200 ml/min. Adsorbent therapy will last 72 hours, changing cartridges every 24 hours. Prior to start, heparinization will be stablished by a 1mg/Kg iv Na heparin bolus plus iv perfusion. Activated Partial Thromboplastin Time (aPTT) control will be performed every 6 hours, with a goal range between 60 and 80 seconds.

Cytokine Adsorption

Eligibility Criteria

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

You may qualify if:

• Age 18 or older
• Positive revere transcription polymerase chain reaction (RT-PCR) for COVID-19 in a respiratory track sample
• Acute (less than 36 hours) onset of moderate to severe ARDS, as defined by Berlin criteria:
• Having pneumonia or worsening respiratory symptoms
• Bilateral pulmonary infiltrates on chest imaging (X-ray of CT scan)
• Pulmonary wedge pressure \<18 mmHg or no clinical signs of left heart failure
• Hypoxemia: arterial oxygen pressure/Fraction of inspired oxygen (PaO2/FiO2 ratio) \<200mmHg, moderate dyspnea with signs of important respiratory workload, tachypnoea \>30bpm
• Rise of inflammatory biomarkers: C-reactive protein (CRP) \>10 mg/L

You may not qualify if:

• Patients with a known contraindication for anticoagulation
• Pregnancy or breast feeding
• Patient already included in another research study
• Decision by a physician that involvement in the study is not in the patient's best interest
• Failure to have patient's authorization. In case of a mechanical intubated patient, lack of authorization from a first line family member
• Multi-organ failure
• Patients treated with Tocilizumab at the time of start filtration

Sponsors & Collaborators

• Manuel Castellà: lead

Study Sites (1)

Hospital Clínic de Barcelona

Barcelona, Spain

RECRUITING

Related Publications (8)

• 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.

  PMID: 31986264 BACKGROUND

• Naicker S, Yang CW, Hwang SJ, Liu BC, Chen JH, Jha V. The Novel Coronavirus 2019 epidemic and kidneys. Kidney Int. 2020 May;97(5):824-828. doi: 10.1016/j.kint.2020.03.001. Epub 2020 Mar 7. No abstract available.

  PMID: 32204907 BACKGROUND

• multicenter collaboration group of Department of Science and Technology of Guangdong Province and Health Commission of Guangdong Province for chloroquine in the treatment of novel coronavirus pneumonia. [Expert consensus on chloroquine phosphate for the treatment of novel coronavirus pneumonia]. Zhonghua Jie He He Hu Xi Za Zhi. 2020 Mar 12;43(3):185-188. doi: 10.3760/cma.j.issn.1001-0939.2020.03.009. Chinese.

  PMID: 32164085 BACKGROUND

• Sheahan TP, Sims AC, Leist SR, Schafer A, Won J, Brown AJ, Montgomery SA, Hogg A, Babusis D, Clarke MO, Spahn JE, Bauer L, Sellers S, Porter D, Feng JY, Cihlar T, Jordan R, Denison MR, Baric RS. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat Commun. 2020 Jan 10;11(1):222. doi: 10.1038/s41467-019-13940-6.

  PMID: 31924756 BACKGROUND

• de Wit E, Feldmann F, Cronin J, Jordan R, Okumura A, Thomas T, Scott D, Cihlar T, Feldmann H. Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection. Proc Natl Acad Sci U S A. 2020 Mar 24;117(12):6771-6776. doi: 10.1073/pnas.1922083117. Epub 2020 Feb 13.

  PMID: 32054787 BACKGROUND

• 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 BACKGROUND

• 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.

  PMID: 32109013 BACKGROUND

• 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 BACKGROUND

MeSH Terms

Conditions

Coronavirus Infections; Respiratory Distress Syndrome

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Study Officials

• Manuel Castellà, MD PhD

  Hospital Clinic of Barcelona

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Manuel Castellà, MD PhD

CONTACT

+34932275515; mcaste@clinic.cat

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD PhDHead of the Cardiovascular Surgery Department, Associate Professor, Principal Investigator

Model Details: This is a two-branch randomized, controlled, uni-center study. Eligible patients will be randomly assigned in a 1:1 ratio to receive cytokine filtration plus standard intensive care, or standard intensive care alone

Study Record Dates

• First Submitted: April 21, 2020
• First Posted: April 24, 2020
• Study Start: April 17, 2020
• Primary Completion: July 1, 2020
• Study Completion: July 1, 2020
• Last Updated: April 24, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)