Pilot Study on Cytokine Filtration in COVID-19 ARDS

Acute Respiratory Distress Syndrome Clinical Trial

— CytokCOVID19  

Official title:

Pilot Study on Cytokine Filtration in COVID-19 ARDS (CytokCOVID19)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04361526
• Other study ID #: HCB/2020/0464
• Status: Recruiting
• Phase: N/A
• Start date: April 17, 2020
• Est. completion date: July 2020

Study information

• Verified date: April 2020
• Source: Hospital Clinic of Barcelona
• Contact: Manuel Castellà, MD PhD
• Phone: +34932275515
• Email: mcaste[@]clinic.cat
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: July 2020
• Est. primary completion date: July 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• Coronavirus Infection
• Coronavirus Infections
• COVID
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn
• Severe Acute Respiratory Syndrome

Intervention

Device:
• Cytokine Adsorption
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.

Locations

Country	Name	City	State
Spain	Hospital Clínic de Barcelona	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Manuel Castellà

Country where clinical trial is conducted

Spain, 

References & Publications (8)

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. — View 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 Feb 28. doi: 10.1056/NEJMoa2002032. [Epub ahead of print] — View 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. Erratum in: Lancet. 2020 Jan 30;:. — View 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. — View 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. — View 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. — View Citation

Sheahan TP, Sims AC, Leist SR, Schäfer 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. — View 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 Mar 13. doi: 10.1001/jamainternmed.2020.0994. [Epub ahead of print] — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	30-day mortality		up to 30 days
Secondary	length of ICU stay (days)		up to 30 days
Secondary	length of hospital stay		up to 30 days
Secondary	Duration of renal replacement and cathecolamines therapies		up to 30 days
Secondary	Need for extracorporeal membrane oxygenation (ECMO) support		up to 30 days
Secondary	multi-organ failure measured by the Sequential Organ Failure Assessment (SOFA) score		up to 30 days (measured on days 0, 1, 2, 3, 4, 5, 6, and the last day of mechanical ventilation)