tetano
Editor, Senior Moderator
Crit Care
. 2022 Feb 21;26(1):48.
doi: 10.1186/s13054-022-03930-4.
Treatment of COVID-19-associated ARDS with mesenchymal stromal cells: a multicenter randomized double-blind trial
Antoine Monsel[SUP] 1 2 3 4 [/SUP], Caroline Hauw-Berlemont[SUP] #[/SUP][SUP] 5 [/SUP], Miryam Mebarki[SUP] #[/SUP][SUP] 6 [/SUP], Nicholas Heming[SUP] 7 [/SUP], Julien Mayaux[SUP] 8 [/SUP], Otriv Nguekap Tchoumba[SUP] 9 10 [/SUP], Jean-Luc Diehl[SUP] 5 11 [/SUP], Alexandre Demoule[SUP] 8 [/SUP], Djillali Annane[SUP] 7 [/SUP], Clémence Marois[SUP] 12 13 [/SUP], Sophie Demeret[SUP] 12 13 [/SUP], Emmanuel Weiss[SUP] 14 15 [/SUP], Guillaume Voiriot[SUP] 16 [/SUP], Muriel Fartoukh[SUP] 16 [/SUP], Jean-Michel Constantin[SUP] 17 [/SUP], Bruno Mégarbane[SUP] 18 [/SUP], Gaëtan Plantefève[SUP] 19 [/SUP], Stéphanie Malard-Castagnet[SUP] 20 [/SUP], Sonia Burrel[SUP] 21 [/SUP], Michelle Rosenzwajg[SUP] 9 10 [/SUP], Nicolas Tchitchek[SUP] 9 10 [/SUP], Hélène Boucher-Pillet[SUP] 22 [/SUP], Guillaume Churlaud[SUP] 22 [/SUP], Audrey Cras[SUP] 6 23 [/SUP], Camille Maheux[SUP] 22 [/SUP], Chloé Pezzana[SUP] 24 [/SUP], Mamadou Hassimiou Diallo[SUP] 25 [/SUP], Jacques Ropers[SUP] 25 [/SUP], Philippe Menasché[SUP] #[/SUP][SUP] 26 [/SUP], Jérôme Larghero[SUP] #[/SUP][SUP] 6 22 [/SUP], APHP STROMA–CoV-2 Collaborative Research Group
Collaborators, Affiliations
Abstract
Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-induced acute respiratory distress syndrome (ARDS) causes high mortality. Umbilical cord-derived mesenchymal stromal cells (UC-MSCs) have potentially relevant immune-modulatory properties, whose place in ARDS treatment is not established. This phase 2b trial was undertaken to assess the efficacy of UC-MSCs in patients with SARS-CoV-2-induced ARDS.
Methods: This multicentre, double-blind, randomized, placebo-controlled trial (STROMA-CoV-2) recruited adults (≥ 18 years) with SARS-CoV-2-induced early (< 96 h) mild-to-severe ARDS in 10 French centres. Patients were randomly assigned to receive three intravenous infusions of 10[SUP]6[/SUP] UC-MSCs/kg or placebo (0.9% NaCl) over 5 days after recruitment. For the modified intention-to-treat population, the primary endpoint was the partial pressure of oxygen to fractional inspired oxygen (PaO[SUB]2[/SUB]/FiO[SUB]2[/SUB])-ratio change between baseline (day (D) 0) and D7.
Results: Among the 107 patients screened for eligibility from April 6, 2020, to October 29, 2020, 45 were enrolled, randomized and analyzed. PaO[SUB]2[/SUB]/FiO[SUB]2[/SUB] changes between D0 and D7 did not differ significantly between the UC-MSCs and placebo groups (medians [IQR] 54.3 [- 15.5 to 93.3] vs 25.3 [- 33.3 to 104.6], respectively; ANCOVA estimated treatment effect 7.4, 95% CI - 44.7 to 59.7; P = 0.77). Six (28.6%) of the 21 UC-MSCs recipients and six of 24 (25%) placebo-group patients experienced serious adverse events, none of which were related to UC-MSCs treatment.
Conclusions: D0-to-D7 PaO[SUB]2[/SUB]/FiO[SUB]2[/SUB] changes for intravenous UC-MSCs-versus placebo-treated adults with SARS-CoV-2-induced ARDS did not differ significantly. Repeated UC-MSCs infusions were not associated with any serious adverse events during treatment or thereafter (until D28). Larger trials enrolling patients earlier during the course of their ARDS are needed to further assess UC-MSCs efficacy in this context.
Trial registration: NCT04333368. Registered 01 April 2020, https://clinicaltrials.gov/ct2/history/NCT04333368 .
. 2022 Feb 21;26(1):48.
doi: 10.1186/s13054-022-03930-4.
Treatment of COVID-19-associated ARDS with mesenchymal stromal cells: a multicenter randomized double-blind trial
Antoine Monsel[SUP] 1 2 3 4 [/SUP], Caroline Hauw-Berlemont[SUP] #[/SUP][SUP] 5 [/SUP], Miryam Mebarki[SUP] #[/SUP][SUP] 6 [/SUP], Nicholas Heming[SUP] 7 [/SUP], Julien Mayaux[SUP] 8 [/SUP], Otriv Nguekap Tchoumba[SUP] 9 10 [/SUP], Jean-Luc Diehl[SUP] 5 11 [/SUP], Alexandre Demoule[SUP] 8 [/SUP], Djillali Annane[SUP] 7 [/SUP], Clémence Marois[SUP] 12 13 [/SUP], Sophie Demeret[SUP] 12 13 [/SUP], Emmanuel Weiss[SUP] 14 15 [/SUP], Guillaume Voiriot[SUP] 16 [/SUP], Muriel Fartoukh[SUP] 16 [/SUP], Jean-Michel Constantin[SUP] 17 [/SUP], Bruno Mégarbane[SUP] 18 [/SUP], Gaëtan Plantefève[SUP] 19 [/SUP], Stéphanie Malard-Castagnet[SUP] 20 [/SUP], Sonia Burrel[SUP] 21 [/SUP], Michelle Rosenzwajg[SUP] 9 10 [/SUP], Nicolas Tchitchek[SUP] 9 10 [/SUP], Hélène Boucher-Pillet[SUP] 22 [/SUP], Guillaume Churlaud[SUP] 22 [/SUP], Audrey Cras[SUP] 6 23 [/SUP], Camille Maheux[SUP] 22 [/SUP], Chloé Pezzana[SUP] 24 [/SUP], Mamadou Hassimiou Diallo[SUP] 25 [/SUP], Jacques Ropers[SUP] 25 [/SUP], Philippe Menasché[SUP] #[/SUP][SUP] 26 [/SUP], Jérôme Larghero[SUP] #[/SUP][SUP] 6 22 [/SUP], APHP STROMA–CoV-2 Collaborative Research Group
Collaborators, Affiliations
- PMID: 35189925
- DOI: 10.1186/s13054-022-03930-4
Abstract
Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-induced acute respiratory distress syndrome (ARDS) causes high mortality. Umbilical cord-derived mesenchymal stromal cells (UC-MSCs) have potentially relevant immune-modulatory properties, whose place in ARDS treatment is not established. This phase 2b trial was undertaken to assess the efficacy of UC-MSCs in patients with SARS-CoV-2-induced ARDS.
Methods: This multicentre, double-blind, randomized, placebo-controlled trial (STROMA-CoV-2) recruited adults (≥ 18 years) with SARS-CoV-2-induced early (< 96 h) mild-to-severe ARDS in 10 French centres. Patients were randomly assigned to receive three intravenous infusions of 10[SUP]6[/SUP] UC-MSCs/kg or placebo (0.9% NaCl) over 5 days after recruitment. For the modified intention-to-treat population, the primary endpoint was the partial pressure of oxygen to fractional inspired oxygen (PaO[SUB]2[/SUB]/FiO[SUB]2[/SUB])-ratio change between baseline (day (D) 0) and D7.
Results: Among the 107 patients screened for eligibility from April 6, 2020, to October 29, 2020, 45 were enrolled, randomized and analyzed. PaO[SUB]2[/SUB]/FiO[SUB]2[/SUB] changes between D0 and D7 did not differ significantly between the UC-MSCs and placebo groups (medians [IQR] 54.3 [- 15.5 to 93.3] vs 25.3 [- 33.3 to 104.6], respectively; ANCOVA estimated treatment effect 7.4, 95% CI - 44.7 to 59.7; P = 0.77). Six (28.6%) of the 21 UC-MSCs recipients and six of 24 (25%) placebo-group patients experienced serious adverse events, none of which were related to UC-MSCs treatment.
Conclusions: D0-to-D7 PaO[SUB]2[/SUB]/FiO[SUB]2[/SUB] changes for intravenous UC-MSCs-versus placebo-treated adults with SARS-CoV-2-induced ARDS did not differ significantly. Repeated UC-MSCs infusions were not associated with any serious adverse events during treatment or thereafter (until D28). Larger trials enrolling patients earlier during the course of their ARDS are needed to further assess UC-MSCs efficacy in this context.
Trial registration: NCT04333368. Registered 01 April 2020, https://clinicaltrials.gov/ct2/history/NCT04333368 .