Design and implementation of the START (STem cells for ARDS Treatment) trial, a phase 1/2 trial of human mesenchymal stem/stromal cells for the treatment of moderate-severe acute respiratory distress syndrome

Background: Despite advances in supportive care, moderate-severe acute respiratory distress syndrome (ARDS) is associated with high mortality rates, and novel therapies to treat this condition are needed. Compelling pre-clinical data from mouse, rat, sheep and ex vivo perfused human lung models support the use of human mesenchymal stem (stromal) cells (MSCs) as a novel intravenous therapy for the early treatment of ARDS. Methods: This article describes the study design and challenges encountered during the implementation and phase 1 component of the START (STem cells for ARDS Treatment) trial, a phase 1/2 trial of bone marrow-derived human MSCs for moderate-severe ARDS. A trial enrolling 69 subjects is planned (9 subjects in phase 1, 60 subjects in phase 2 treated with MSCs or placebo in a 2:1 ratio). Results: This report describes study design features that are unique to a phase 1 trial in critically ill subjects and the specific challenges of implementation of a cell-based therapy trial in the ICU. Conclusions: Experience gained during the design and implementation of the START study will be useful to investigators planning future phase 1 clinical trials based in the ICU, as well as trials of cell-based therapy for other acute illnesses. Trial registration Clinical Trials Registration: NCT01775774 and NCT02097641

Dialysis dose, nutrition and growth among pediatric patients on peritoneal dialysis Dosis de diálisis nutrición y crecimiento en diálisis peritoneal pediátrica

Background: Stunting is common among pediatric patients on peritoneal dialysis. Aim: To stablish the best profile for urea kinetic variables associated to growth in children on chronic peritoneal dialysis (PD). Patients and Methods: Twenty patients, aged 1 month to 14 years, 23 males, were followed for 6-12 months, with monthly measurements of weight/age and height/age Z score; plasma creatinine, BUN, protein and albumin and urine and dialysate urea nitrogen, creatinine, protein and albumin. Minimum total Kt/V was 2.1. Dialysis dose (Kt/V), Protein Equivalent of Urea Nitrogen Appearence (PNA), Protein Catabolic Rite (PCR) and Nitrogen Balance (NB) were calculated. To identify the variable(s) associated to growth, the Tree Classification Model (CART) Enterprise Miner 8.1 was applied. Results: Mean total/residual Kt/V: 3.4±1.3/1.69±1.27; Daily Protein Intake (DPI) was 3.25±1.27 g/kg/day. nPNA, PCR and NB were 1.37±0.44, 0.84±0.33 and 1.86±1.25 g/kg/day, respectively. Mean heigth/age Z s