Treatment of COVID-19-associated ARDS with mesenchymal stromal cells: a multicenter randomized double-blind trial

Monsel, Antoine; Hauw-Berlemont, Caroline; Mebarki, Miryam; Heming, Nicholas; Mayaux, Julien; Nguekap Tchoumba, Otriv; Diehl, Jean-Luc; Demoule, Alexandre; Annane, Djillali; Marois, Clémence; Demeret, Sophie; Weiss, Emmanuel; Voiriot, Guillaume; Fartoukh, Muriel; Constantin, Jean-Michel; Mégarbane, Bruno; Plantefève, Gaëtan; Malard-Castagnet, Stéphanie; Burrel, Sonia; Rosenzwajg, Michelle; Tchitchek, Nicolas; Boucher-Pillet, Hélène; Churlaud, Guillaume; Cras, Audrey; Maheux, Camille; Pezzana, Chloé; Diallo, Mamadou Hassimiou; Ropers, Jacques; Menasché, Philippe; Larghero, Jérôme

doi:10.1186/s13054-022-03930-4

Critical Care

Table 4 Main clinical outcomes

From: Treatment of COVID-19-associated ARDS with mesenchymal stromal cells: a multicenter randomized double-blind trial

Primary endpoint	UC-MSCs (n = 21)	Placebo (n = 24)	Estimate (95% CI)	p value
PaO₂/FiO₂-ratio change D0–D7(principal analysis)	54.3 [− 15.5; 93.3]	25.3 [− 33.3; 104.6]	7.4 (− 44.7; 59.7)	0.77
PaO₂/FiO₂-ratio change D0–D7(sensitivity analysis)	54.3 [− 15.5; 93.3]	25.3 [− 33.3; 83.1]	12.5 (− 33.8; 56.7)	0.59

Secondary endpoints	UC-MSCs (n = 21)	Placebo (n = 24)	Median difference (95% CI), HR or sub-HR	p value
PaO₂/FiO₂-ratio change D0–D14	11.0 [− 39; 72.7]	28.2 [− 1; 67.3]	1.69 (− 82.1; 90.7)	1
Ventilation-free days to D28, n	17.0 [0; 25.0]	12.0 [0; 19.7]	0.5 (− 3.0; 8.0)	0.61
Ventilation duration to D28, n	9.0 [3.0; 20.0]	10 [5.7; 20.0]	− 2.5 (− 8.0; 3.0)	0.38
Ventilation duration to D28 for recipients of 3 UC-MSC doses	11.0 [6.0; 24.0]	13.0 [7.0; 22.0]	− 0.5 (− 8; 6)	0.79
SOFA-score change D0–D7	− 1.5 [− 2; 0.75]	− 2 [− 3.2; 0.2]	0.5 (− 2.0; 3.0)	0.60
SOFA-score change D0–D14	− 0.5 [− 1.2; 1.0]	− 3.0 [− 3; − 1.0]	1.5 (− 1.0; 5.0)	0.12
Organ-failure–free days to D14, n	3.0 [0; 6.0]	2.0 [0; 9.0]	− 0.5 (− 4.0; 3.0)	0.96
Organ-failure–free days to D28, n	16.0 [2.0; 20.0]	15.0 [0.75; 23]	− 0.5 (− 7.0; 4.0)	0.68
Days to reach PaO₂/FiO₂ > 200	5.0 [0; 16.0]	2.5 [0; 6.5]	0.74 [0.3; 1.6]	0.44
Days to reach PaO₂/FiO₂ > 300	12.0 [7.0; 23.0]	15.0 [5.0; 27.0]	1.1 [0.5; 2.3]	0.87
Days to ICU discharge^a	15.0 [8.0; NA]	13.0 [5.5; 27]	0.8 [0.4; 1.7]	0.59
Days to weaning^b	13.0 [9.0; NA]	17.0 [8.0; NA]	1.3 [0.5; 3.3]	0.55
Compliance change D0–D7	− 3.6 [− 11.8; 4.7]	− 0.1 [− 4.5; 2.4]	0.4 (− 24.7; 25.5)	1
Compliance change D0–D14	− 3.0 [− 3.0; − 3.0]	2.5 [− 0.9; 11.7]	− 5.52 (− 35.4; 1.1)	0.8
Driving pressure change D0–D7	0.5 [− 3.2; 4.2]	0.5 [− 1.2; 2.2]	0 (− 13.0; 13.0)	1
Driving pressure change D0–D14	1.0 [1.0; 1.0]	− 1.5 [− 2.0; 0.2]	2.5 (− 3.0; 3.0)	0.8
D28 mortality	5.0 (26.3%)	4.0 (18.2%)	2.0 (0.5; 8.5)	0.36

Values are expressed as median [interquartile range], or number (%), unless stated otherwise
CI confidence interval, D day, HR hazard ratio, ICU intensive care unit, NA not applicable, PaO₂/FiO₂ ratio of partial pressure of oxygen to fractional inspired oxygen, PEEP positive end-expiratory pressure, SOFA Sepsis-related Organ-Failure Assessment, UC-MSCs umbilical cord-derived mesenchymal stromal cells
^aCensored at day of death for patients having died before D28 and censored at D28 for those patients still in the ICU at D28
^bEstimated for the subgroup of patients ventilated at randomization, i.e., 31 patients (11 in CSM-CO group and 20 in placebo group). At Day 28, 6 had died (and censored at time of death), 17 were weaned, and 8 were alive and not weaned yet (censored at D28)

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