Clinical trial NCT04361526: Pilot Study on Cytokine Filtration in COVID-19 ARDS
Official title: Pilot Study on Cytokine Filtration in COVID-19 ARDS (CytokCOVID19)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Coronavirus Infection
Acute Respiratory Distress Syndrome
COVID
Keywords: COVID
ARDS
Coronavirus
Lead sponsor: Hospital Clinic of Barcelona
Sponsor class: OTHER
First posted: 2020-04-24
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Age 18 or older
2. Positive revere transcription polymerase chain reaction (RT-PCR) for COVID-19 in a respiratory track sample
3. 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
4. Rise of inflammatory biomarkers: C-reactive protein (CRP) \>10 mg/L

Exclusion Criteria:

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

Primary outcomes:
measure: Mechanical ventilation-free days
timeFrame: up to 28days
Secondary outcomes:
measure: 30-day mortality
timeFrame: up to 30 days
measure: length of ICU stay (days)
timeFrame: up to 30 days
measure: length of hospital stay
timeFrame: up to 30 days
measure: Duration of renal replacement and cathecolamines therapies
timeFrame: up to 30 days
measure: Need for extracorporeal membrane oxygenation (ECMO) support
timeFrame: up to 30 days
measure: multi-organ failure measured by the Sequential Organ Failure Assessment (SOFA) score
timeFrame: up to 30 days (measured on days 0, 1, 2, 3, 4, 5, 6, and the last day of mechanical ventilation)
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
Study officials:
affiliation: Hospital Clinic of Barcelona
name: Manuel Castellà, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
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: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
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: 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.