Polyvalent Immunoglobulin in COVID-19 Related ARds

NCT04350580 | Completed Phase 3 DMC

• 2 other identifiers: D20-P0132020-001570-30
• Study Type: interventional
• Target: 146
• Locations: 1 country
• Sites: 42

Brief Summary

As of 30/03/2020, 715600 people have been infected with COVID-19 worldwide and 35500 people died, essentially due to respiratory distress syndrome (ARDS) complicated in 25% of the with acute renal failure. No specific pharmacological treatment is available yet. The lung lesions are related to both the viral infection and to an intense inflammatory reaction. Because of it's action, as an immunomodulatory agent that can attenuate the inflammatory reaction and also strengthen the antiviral response, it is proposed to evaluate the effectiveness and safety of intravenous immunoglobulin administration (IGIV) in patients developing ARDS post-SARS-CoV2. IGIV modulates immunity, and this effect results in a decrease of pro-inflammatory activity, key factor in the ARDS related to the COVID-19. It should be noted that IGIV is part of the treatments in various diseases such as autoimmune and inflammatory diffuse interstitial lung diseases. In addition, they have been beneficial in the post-influenza ARDS but also have been in 3 cases of post-SARS-CoV2 ARDS. IGIV is a treatment option because it is well tolerated, especially concerning the kidney. These elements encourage a placebo-controlled trial testing the benefit of IGIV in ARDS post-SARS-CoV2.

Conditions

Acute Respiratory Distress Syndrome; COVID-19

Keywords

acute respiratory distress syndrome; COVID-19; SARS-CoV-2; Immunoglobulin

Outcome Measures

Primary Outcomes (1)

• Ventilator-free days

  Sum of the days the patient did not receive VM, but if death occurs before D28, the score is zero

  28 days

Secondary Outcomes (15)

• Mortality

  28 and 90 days

• Sequential Organ Failure Assessment Score

  Days 1, 3, 7, 14, 21 and 28

• P/F ratio

  Days 1, 3, 7, 14, 21 and 28

• Lung compliance

  Days 1, 3, 7, 14, 21 and 28

• Radiological score

  Days 1, 3, 7, 14, 21 and 28

Study Arms (2)

Intervention - IGIV

EXPERIMENTAL

Participants in the intervention group will receive a 2g/Kg infusion of human immunoglobulin which should be started before the 96th hours after the start of mechanical ventilation in 4 injections of 0.5 g/Kg over 4 consecutive days.

Drug: Human immunoglobulin

Placebo

PLACEBO COMPARATOR

Participants of the placebo group will receive an equivalent volume of sodium chloride 0.9% for the same duration.

Drug: Placebo

Interventions

Human immunoglobulin DRUG

Human immunoglobulin 2g/kg over 4 days (0.5g/kg/d)

Also known as: Clairyg

Intervention - IGIV

Placebo DRUG

Sodium chloride 0.9% in the same volume and over the same time as the immunoglobulin

Also known as: Sodium chloride 0.9%

Placebo

Eligibility Criteria

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

You may qualify if:

• Any patient in intensive care:
• Receiving invasive mechanical ventilation for less than 72 hours
• ARDS meeting the Berlin criteria
• PCR-proven SARS-CoV-2 infection
• Patient, family or deferred consent (emergency clause)
• Affiliation to a social security scheme (or exemption from affiliation)

You may not qualify if:

• Allergy to polyvalent immunoglobulins
• Pregnant woman or minor patient
• Known IgA deficiency
• Patient with renal failure on admission defined by a 3 times baseline creatinine or creatinine \>354 micromol/L or a diuresis of less than 0.3 mL/Kg for 24 hours or anuria for 12 hours
• Participation in another interventional trial

Sponsors & Collaborators

• Centre Hospitalier St Anne: lead
• Groupe Hospitalier Universitaire Paris psychiatrie & neurosciences: collaborator
• Laboratoire français de Fractionnement et de Biotechnologies: collaborator

Study Sites (42)

CHU Sud Amiens

Amiens, France

Location

CHU Angers

Angers, France

Location

Service de réanimation polyvalente, rond point de Girac

Angoulême, France

Location

CH Victor Dupouy

Argenteuil, France

Location

CH Aulnay

Aulnay-sous-Bois, France

Location

Centre hospitalier de Béthune

Beuvry, France

Location

Hopital Avicenne

Bobigny, France

Location

CH-Nord-Ardennes

Charleville-Mézières, France

Location

CH Chalons en champagne

Châlons-en-Champagne, France

Location

Hopital d'instruction des armées Percy

Clamart, France

Location

Centre Hospitalier de Dieppe

Dieppe, France

Location

CH Etampes

Étampes, France

Location

Hôpital Raymond Poincaré

Garches, France

Location

CHU de Grenoble

Grenoble, France

Location

Grand hopital de l'est Francilien - site de Jossigny

Jossigny, France

Location

Hopital Robert Boulin

Libourne, France

Location

Pôle de Médecine intensive/réanimation Hôpital Salengro, CHRU de Lille

Lille, France

Location

Groupement Hospitalier Edouar Herriot

Lyon, France

Location

Hôpital de la Croix Rousse Novembre 2019

Lyon, France

Location

Hopital Jacques Cartier

Massy, France

Location

Hopital Jacques Monod

Montivilliers, France

Location

Service de Médecine Intensive-Réanimation, CHU

Nantes, France

Location

CHR Orléans

Orléans, France

Location

Centre Hospitalier Sainte-Anne

Paris, France

Location

CHU Lariboisiere

Paris, France

Location

CHU Pitié Salpétriere Service de réanimation chirurgicale

Paris, France

Location

CHU Saint Antoine

Paris, France

Location

Fondation ophtalmologique Rotschild

Paris, France

Location

Hôpital Paris Saint-Joseph

Paris, France

Location

Hôpital Pitié Salpêtrière

Paris, France

Location

Institut Mutualiste Montsouris

Paris, France

Location

CHU Poitiers

Poitiers, France

Location

CHU Robert Débré

Reims, France

Location

CH Poissy

Saint-Germain-en-Laye, France

Location

Groupe hospitalier Saint Vincent

Strasbourg, France

Location

Hôpital de Hautepierre

Strasbourg, France

Location

Hopital de Tarbes

Tarbes, France

Location

Hôpital Nord Franche-Comté

Trévenans, France

Location

CH Valenciennes

Valenciennes, France

Location

Chu Nancy - Brabois

Vandœuvre-lès-Nancy, France

Location

Hopital de Vannes

Vannes, France

Location

Institut Gustave Roussy

Villejuif, France

Location

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

• Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, Liu S, Zhao P, Liu H, Zhu L, Tai Y, Bai C, Gao T, Song J, Xia P, Dong J, Zhao J, Wang FS. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020 Apr;8(4):420-422. doi: 10.1016/S2213-2600(20)30076-X. Epub 2020 Feb 18. No abstract available.

  PMID: 32085846 BACKGROUND

• Chaigne B, Mouthon L. Mechanisms of action of intravenous immunoglobulin. Transfus Apher Sci. 2017 Feb;56(1):45-49. doi: 10.1016/j.transci.2016.12.017. Epub 2016 Dec 30.

  PMID: 28161150 BACKGROUND

• Arish N, Eldor R, Fellig Y, Bogot N, Laxer U, Izhar U, Rokach A. Lymphocytic interstitial pneumonia associated with common variable immunodeficiency resolved with intravenous immunoglobulins. Thorax. 2006 Dec;61(12):1096-7. doi: 10.1136/thx.2004.029819.

  PMID: 17114373 BACKGROUND

• Oates-Whitehead RM, Baumer JH, Haines L, Love S, Maconochie IK, Gupta A, Roman K, Dua JS, Flynn I. Intravenous immunoglobulin for the treatment of Kawasaki disease in children. Cochrane Database Syst Rev. 2003;2003(4):CD004000. doi: 10.1002/14651858.CD004000.

  PMID: 14584002 BACKGROUND

• Alejandria MM, Lansang MA, Dans LF, Mantaring JB 3rd. Intravenous immunoglobulin for treating sepsis, severe sepsis and septic shock. Cochrane Database Syst Rev. 2013 Sep 16;2013(9):CD001090. doi: 10.1002/14651858.CD001090.pub2.

  PMID: 24043371 BACKGROUND

• Mazeraud A, Jamme M, Mancusi RL, Latroche C, Megarbane B, Siami S, Zarka J, Moneger G, Santoli F, Argaud L, Chillet P, Muller G, Bruel C, Asfar P, Beloncle F, Reignier J, Vinsonneau C, Schimpf C, Amour J, Goulenok C, Lemaitre C, Rohaut B, Mateu P, De Rudnicki S, Mourvillier B, Declercq PL, Schwebel C, Stoclin A, Garnier M, Madeux B, Gaudry S, Bailly K, Lamer C, Aegerter P, Rieu C, Sylla K, Lucas B, Sharshar T. Intravenous immunoglobulins in patients with COVID-19-associated moderate-to-severe acute respiratory distress syndrome (ICAR): multicentre, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med. 2022 Feb;10(2):158-166. doi: 10.1016/S2213-2600(21)00440-9. Epub 2021 Nov 11.

  PMID: 34774185 DERIVED

• Mazeraud A, Goncalves B, Aegerter P, Mancusi L, Rieu C, Bozza F, Sylla K, Siami S, Sharshar T. Effect of early treatment with polyvalent immunoglobulin on acute respiratory distress syndrome associated with SARS-CoV-2 infections (ICAR trial): study protocol for a randomized controlled trial. Trials. 2021 Feb 28;22(1):170. doi: 10.1186/s13063-021-05118-7.

  PMID: 33648563 DERIVED

MeSH Terms

Conditions

Respiratory Distress Syndrome; COVID-19

Interventions

Immunoglobulins, Intravenous; Sodium Chloride

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections

Intervention Hierarchy (Ancestors)

Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Tarek Sharshar, MD, PHD

  Centre Hospitalier Sainte Anne

  STUDY CHAIR

• Aurélien Mazeraud, MD, PHD

  Centre Hospitalier Sainte Anne

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: The double blinding will be provided by the hospital pharmacy of each establishment with the help of opaque sleeves to mask the product packaging and should be returned to the pharmacy when empty.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The participant will be randomized to either the group of treatment with IVIG or the placebo group. Participants in the treatment group will receive infusions of polyvalent immunoglobulins for 4 consecutive days. Participants in the placebo group will receive an equivalent volume of sodium chloride 0.9% for the same duration.

Study Record Dates

• First Submitted: April 8, 2020
• First Posted: April 17, 2020
• Study Start: April 11, 2020
• Primary Completion: November 20, 2020
• Study Completion: February 20, 2021
• Last Updated: August 19, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (42)