Preprints with The Lancet is part of SSRN´s First Look, a place where journals identify content of interest prior to publication. Authors have opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early stage research papers that have not been peer-reviewed. The findings should not be used for clinical or public health decision making and should not be presented to a lay audience without highlighting that they are preliminary and have not been peer-reviewed. For more information on this collaboration, see the comments published in The Lancet about the trial period, and our decision to make this a permanent offering, or visit The Lancet´s FAQ page, and for any feedback please contact firstname.lastname@example.org.
Umbilical Cord Mesenchymal Stem Cells for COVID-19 ARDS: A Double Blind, Phase 1/2a, Randomized Controlled Trial
24 Pages Posted: 26 Oct 2020More...
Background: Acute Respiratory Distress Syndrome (ARDS) in COVID-19 is associated with high mortality. Mesenchymal Stem Cells (MSC) are potent immunomodulatory cells. The aim of this study was to determine safety and explore efficacy of Umbilical Cord (UC)-MSC infusions in COVID-19 ARDS.
Methods: A double-blind, phase 1/2a, randomized, controlled trial was performed in subjects with ARDS secondary to COVID-19, at a single institution in Miami, Florida, USA. Randomization and stratification by ARDS severity was used to foster balance among groups. Participants received two intravenous infusions of 100x106 UC-MSC, or vehicle, at day 0 and 3. The primary endpoint was safety, defined by occurrence of pre-specified infusion associated adverse events, along with adverse events during 28 day follow-up. All subjects were analyzed under an intention to treat design. Exploratory efficacy endpoints included survival at 28 days and time to recovery.
Findings: 24 subjects (12 per group) were recruited between April 25 and July 21 2020. At 28 days post last infusion, patient survival was 91% and 42% in the UC-MSC and Control groups, respectively (p=0.015). No serious adverse events (SAEs) were observed related to UC-MSC infusions. There was no observed difference in number of subjects experiencing infusion-associated adverse events. Treatment unrelated SAEs were reported in 2 and 8 patients in the UC-MSC and Control groups, respectively (p=0.04). UC-MSC treatment was associated with increased SAE-free survival (p=0.008) and decreased time to recovery (p=0.03) compared to controls.
Interpretation: UC-MSC infusions in COVID-19 subjects with ARDS were safe and associated with fewer SAEs, compared to control. Further, exploratory efficacy analyses provide preliminary evidence of reduction in mortality and time to recovery. Notwithstanding sample size limitations of this trial, the observed findings strongly support further investigation in a larger trial designed to estimate and test for efficacy.
Trial Registration: (ClinicalTrials.gov NCT04355728).
Funding Statement: The trial was funded by the Barilla Group and Family, The Cure Alliance, the Fondazione Silvio Tronchetti Provera, the Simkins Family Foundation, the North America’s Building Trades Unions, and the Diabetes Research Institute Foundation. This publication was supported by the Clinical Translational Research Site Grants Number UL1TR000460 and UL1TR002736 from the National Center for Advancing Translational Sciences (NCATS).
Declaration of Interests: The authors declare no competing interests.
Ethics Approval Statement: Ethics Committee Approval by the regulatory and institutional review boards were obtained by the Western Institutional Review Board (WIRB) and UM Human Subject Research Office/Institutional Review Board, in accordance with local institutional requirements.
Keywords: Mesenchymal Stem Cells, Mesenchymal Stromal Cells, MSC, Umbilical Cord, Subepitelial Lining, UC-MSC, COVID-19, Coronavirus, SARS-CoV-2, ARDS, acute respiratory distress syndrome, RCT, Randomised, Randomized, Controlled Trial, clinical trial, Trial, Phase 1/2a, Double Blind
Suggested Citation: Suggested Citation