Coronavirus InfectionCytokCOVID19NCT04361526
Pilot Study on Cytokine Filtration in COVID-19 ARDS
A study testing Cytokine Adsorption in people with Coronavirus Infection and Acute Respiratory Distress Syndrome, run by Manuel Castellà at 1 site in Spain.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronavirus Infection, Acute Respiratory Distress Syndrome, COVID
- What is being tested?
- Cytokine Adsorption
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteSpain
- Study dates
- 17 Apr 2020to Jul 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Spain1 site, 1 recruiting
- Recruiting
Hospital Clínic de Barcelona
Barcelona
Manuel Castellà, MD PhD, +34932275515, mcaste@clinic.cat
About this study
Official title: Pilot Study on Cytokine Filtration in COVID-19 ARDS (CytokCOVID19)
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.
- Being tested
- Cytokine Adsorption
- Keywords
- COVID, ARDS, Coronavirus
- Medical subject headings
- Coronavirus Infections, Respiratory Distress Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cytokine AdsorptionDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| Control | No intervention | standard intensive care alone |
| Cytokine Adsorption | Experimental | cytokine adsorption plus standard intensive care Receives: Device: Cytokine Adsorption |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: up to 28days
Secondary outcomes (6)
30-day mortality
Measured: up to 30 days
length of ICU stay (days)
Measured: up to 30 days
length of hospital stay
Measured: up to 30 days
Duration of renal replacement and cathecolamines therapies
Measured: up to 30 days
Need for extracorporeal membrane oxygenation (ECMO) support
Measured: up to 30 days
multi-organ failure measured by the Sequential Organ Failure Assessment (SOFA) score
Measured: up to 30 days (measured on days 0, 1, 2, 3, 4, 5, 6, and the last day of mechanical ventilation)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2020
- Study start17 Apr 2020
- Primary completionJul 2020 (estimated)
- Study completionJul 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Coronavirus InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Manuel Castellà
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Manuel Castellà, Hospital Clinic of Barcelona
- Investigators
- Manuel Castellà, MD PhD, Principal investigator, Hospital Clinic of Barcelona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04361526
- Sponsor's protocol ID
- HCB/2020/0464
- Acronym
- CytokCOVID19
- Status last verified
- Apr 2020
- First submitted
- 21 Apr 2020
- Last updated
- 24 Apr 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 31986264Naicker 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.
PubMed 32204907multicenter 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.
PubMed 32164085Sheahan 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.
PubMed 31924756de 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.
PubMed 32054787Wu 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.
PubMed 32167524Guan 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.
PubMed 32109013Mehta 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.
PubMed 32192578
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study on Cytokine Filtration in COVID-19 ARDS (CytokCOVID19)
- ClinicalTrials.gov ID
- NCT04361526
- Acronym / sponsor ID
- CytokCOVID19 / HCB/2020/0464
- Keywords
- COVID, ARDS, Coronavirus
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Manuel CastellàUniversity, hospital or other
- Study start
- 17 Apr 2020 (actual)
- Primary completion
- Jul 2020 (estimated)
- Study completion
- Jul 2020 (estimated)
- First posted
- 24 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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
| Arm | Type | Receives |
|---|---|---|
| Control | No intervention | –standard intensive care alone |
| Cytokine Adsorption | Experimental | Device: Cytokine Adsorptioncytokine adsorption plus standard intensive care |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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:
- Rise of inflammatory biomarkers: C-reactive protein (CRP) >10 mg/L
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cytokine AdsorptionCytokine 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. | Device | Cytokine Adsorption |
Primary outcome
Mechanical ventilation-free days
Time frame: up to 28days
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
6 secondary outcomes
30-day mortality
Time frame: up to 30 days
length of ICU stay (days)
Time frame: up to 30 days
length of hospital stay
Time frame: up to 30 days
Duration of renal replacement and cathecolamines therapies
Time frame: up to 30 days
Need for extracorporeal membrane oxygenation (ECMO) support
Time frame: up to 30 days
multi-organ failure measured by the Sequential Organ Failure Assessment (SOFA) score
Time frame: up to 30 days (measured on days 0, 1, 2, 3, 4, 5, 6, and the last day of mechanical ventilation)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2020.
- Background: PubMed 31986264Huang 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.
- Background: PubMed 32204907Naicker 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.
- Background: PubMed 32164085multicenter 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.
- Background: PubMed 31924756Sheahan 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.
- Background: PubMed 32054787de 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.
- Background: PubMed 32167524Wu 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.
- Background: PubMed 32109013Guan 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.
- Background: PubMed 32192578Mehta 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Manuel Castellà, MD PhD principal investigator
Hospital Clinic of Barcelona
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cytokine Adsorption in people with Coronavirus Infection and Acute Respiratory Distress Syndrome, run by Manuel Castellà at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 24 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Manuel Castellà, MD PhD (+34932275515, mcaste@clinic.cat), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mechanical ventilation-free days (time frame: up to 28days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04361526, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2020.