NCT04369820

Brief Summary

The pathophysiology of ARDS is linked to an uncontrolled inflammatory response at the level of alveolo-capillary membrane, mediated by neutrophils and mononuclear cells. The complement system and anaphylatoxin C5a have shown central role in the recruitment of these pro-inflammatory cells and more broadly in the genesis of cytokinic storm syndrome. C5a acts via receptors C5aR and C5L2. This is a preliminary study aimed at studying the expression of the C5a receptor on myeloid cells in peripheral blood of patients with ARDS secondary to COVID-19. This study has of primary objective to show there is an overexpression of the C5a receptor in patients with ARDS secondary to COVID-19 compared to control patients (patients with COVID-19 without respiratory distress and healthy volunteers). The medium-term objective is to develop a clinical trial to test the effectiveness of anti-C5aR antibody in this condition.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
61

participants targeted

Target at P25-P50 for not_applicable covid19

Timeline
Completed

Started Mar 2020

Longer than P75 for not_applicable covid19

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 31, 2020

Completed
29 days until next milestone

First Submitted

Initial submission to the registry

April 29, 2020

Completed
1 day until next milestone

First Posted

Study publicly available on registry

April 30, 2020

Completed
5 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 30, 2020

Completed
2.9 years until next milestone

Study Completion

Last participant's last visit for all outcomes

August 9, 2023

Completed
Last Updated

August 14, 2023

Status Verified

August 1, 2023

Enrollment Period

6 months

First QC Date

April 29, 2020

Last Update Submit

August 9, 2023

Conditions

COVID-19

Keywords

COVID-19ARDSC5a receptors

Outcome Measures

Primary Outcomes (1)

  • Show an overexpression of C5a receptor in patients with ARDS secondary to COVID-19 compared to control patients (patients with COVID-19 without respiratory distress and healthy volunteers).

    The endpoint is the expression of the C5a receptor (C5aR) in peripheral blood myeloid cells, expressed as a percentage of cells expressing C5a receptor and as median fluorescence intensity (MFI), during the first 72 hours of patient management in resuscitation unit.

    72 hours

Study Arms (1)

COVID-19 PATIENTS

EXPERIMENTAL

Two blood samples (40mL) at 2 different points in time: 1. Within the first 72 hours of medical care in resuscitation unit or department. 2. Between the 5th and the 10th day of medical care (ideally at the end of the first week) or on the day of discharge of patient if it is earlier, or of death if it takes place earlier.

Other: draw blood

Interventions

draw bloodOTHER

40 mL blood sample will be taken within the first three days of hospitalization, a second sample will be taken between the 5th and 10th day of hospitalization and a third sample will be taken on the 10th day of hospitalization or the day of discharge if earlier.

COVID-19 PATIENTS

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • For patients in resuscitation unit with ARDS linked to COVID-19:
  • Patient under invasive mechanical ventilation
  • PaO2 / FiO2 \<300
  • PCR SARS-CoV-2 positive in a pharyngeal or respiratory sample
  • For control patients with COVID-19 without ARDS
  • Oxygen flow always less than 5 L / min
  • PCR SARS-CoV-2 positive in a pharyngeal or respiratory sample
  • No passage in resuscitation unit
  • Favorable evolution

You may not qualify if:

  • Minors
  • Patient deprived of liberty
  • Patient's refusal to participate at study
  • Patient for whom therapeutic limitation measures such as non-admission to intensive care have been issued
  • Medullar aplasia

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Assistance Publique Hôpitaux de Marseille

Marseille, 13354, France

Location

Related Publications (13)

  • Kinross P, Suetens C, Dias JG, Alexakis L, Wijermans A, Colzani E, Monnet DL; European Centre for Disease Prevention and Control (ECDC) Public Health Emergency Team; ECDC Public Health Emergency Team. Rapidly increasing cumulative incidence of coronavirus disease (COVID-19) in the European Union/European Economic Area and the United Kingdom, 1 January to 15 March 2020. Euro Surveill. 2020 Mar;25(11):2000285. doi: 10.2807/1560-7917.ES.2020.25.11.2000285. Epub 2020 Mar 16.

    PMID: 32186277BACKGROUND

  • Parmet WE, Sinha MS. Covid-19 - The Law and Limits of Quarantine. N Engl J Med. 2020 Apr 9;382(15):e28. doi: 10.1056/NEJMp2004211. Epub 2020 Mar 18. No abstract available.

    PMID: 32187460BACKGROUND

  • Gostin LO, Hodge JG Jr, Wiley LF. Presidential Powers and Response to COVID-19. JAMA. 2020 Apr 28;323(16):1547-1548. doi: 10.1001/jama.2020.4335. No abstract available.

    PMID: 32186661BACKGROUND

  • Grasselli G, Pesenti A, Cecconi M. Critical Care Utilization for the COVID-19 Outbreak in Lombardy, Italy: Early Experience and Forecast During an Emergency Response. JAMA. 2020 Apr 28;323(16):1545-1546. doi: 10.1001/jama.2020.4031. No abstract available.

    PMID: 32167538BACKGROUND

  • Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062. doi: 10.1016/S0140-6736(20)30566-3. Epub 2020 Mar 11.

    PMID: 32171076BACKGROUND

  • 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: 32109013BACKGROUND

  • Herrero R, Sanchez G, Lorente JA. New insights into the mechanisms of pulmonary edema in acute lung injury. Ann Transl Med. 2018 Jan;6(2):32. doi: 10.21037/atm.2017.12.18.

    PMID: 29430449BACKGROUND

  • Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, Ruan L, Song B, Cai Y, Wei M, Li X, Xia J, Chen N, Xiang J, Yu T, Bai T, Xie X, Zhang L, Li C, Yuan Y, Chen H, Li H, Huang H, Tu S, Gong F, Liu Y, Wei Y, Dong C, Zhou F, Gu X, Xu J, Liu Z, Zhang Y, Li H, Shang L, Wang K, Li K, Zhou X, Dong X, Qu Z, Lu S, Hu X, Ruan S, Luo S, Wu J, Peng L, Cheng F, Pan L, Zou J, Jia C, Wang J, Liu X, Wang S, Wu X, Ge Q, He J, Zhan H, Qiu F, Guo L, Huang C, Jaki T, Hayden FG, Horby PW, Zhang D, Wang C. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020 May 7;382(19):1787-1799. doi: 10.1056/NEJMoa2001282. Epub 2020 Mar 18.

    PMID: 32187464BACKGROUND

  • Gralinski LE, Sheahan TP, Morrison TE, Menachery VD, Jensen K, Leist SR, Whitmore A, Heise MT, Baric RS. Complement Activation Contributes to Severe Acute Respiratory Syndrome Coronavirus Pathogenesis. mBio. 2018 Oct 9;9(5):e01753-18. doi: 10.1128/mBio.01753-18.

    PMID: 30301856BACKGROUND

  • Wang R, Xiao H, Guo R, Li Y, Shen B. The role of C5a in acute lung injury induced by highly pathogenic viral infections. Emerg Microbes Infect. 2015 May;4(5):e28. doi: 10.1038/emi.2015.28. Epub 2015 May 6.

    PMID: 26060601BACKGROUND

  • Jiang Y, Zhao G, Song N, Li P, Chen Y, Guo Y, Li J, Du L, Jiang S, Guo R, Sun S, Zhou Y. Blockade of the C5a-C5aR axis alleviates lung damage in hDPP4-transgenic mice infected with MERS-CoV. Emerg Microbes Infect. 2018 Apr 24;7(1):77. doi: 10.1038/s41426-018-0063-8.

    PMID: 29691378BACKGROUND

  • Stevens JH, O'Hanley P, Shapiro JM, Mihm FG, Satoh PS, Collins JA, Raffin TA. Effects of anti-C5a antibodies on the adult respiratory distress syndrome in septic primates. J Clin Invest. 1986 Jun;77(6):1812-6. doi: 10.1172/JCI112506.

    PMID: 3711336BACKGROUND

  • Czermak BJ, Sarma V, Pierson CL, Warner RL, Huber-Lang M, Bless NM, Schmal H, Friedl HP, Ward PA. Protective effects of C5a blockade in sepsis. Nat Med. 1999 Jul;5(7):788-92. doi: 10.1038/10512.

    PMID: 10395324BACKGROUND

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, ViralPneumoniaRespiratory Tract InfectionsInfectionsVirus DiseasesCoronavirus InfectionsCoronaviridae InfectionsNidovirales InfectionsRNA Virus InfectionsLung DiseasesRespiratory Tract Diseases

Study Officials

  • Emilie EGP GARRIDO-PRADALIE

    Assistance Publique Hôpitaux de Marseille

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
OTHER
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 29, 2020

First Posted

April 30, 2020

Study Start

March 31, 2020

Primary Completion

September 30, 2020

Study Completion

August 9, 2023

Last Updated

August 14, 2023

Record last verified: 2023-08

Locations

FR(1)