The First 400 Patients PROSPECT Meeting June 13, 2016 Jennie Johnstone, MD, PhD, FRCPC St. Joseph’s Health Center Public Health Ontario

Context and Mandate At Public Health Ontario, our mandate is to provide scientific and technical advice and support to clients working in government, public health, health care, and related sectors. Broad range of activities, notably: knowledge synthesis and best practice generation, laboratory services, surveillance and population health assessment, and research. 2

PHO IPAC Research and Evaluation Activities PHO’s IPAC Department pursues scientific and research activities, both independently and in response to issues emerging from the field Research focused on range of preventing healthcare associated infections: –Clostridium difficile infection –Ventilator acquired pneumonia –Vancomycin Resistant Enterococcus (VRE) 3

In critically ill patients expected to be mechanically ventilated for ≥72 hours, does Lactobacillus rhamnosus GG prevent VAP, other infections, diarrhea and other clinically important outcomes when compared to placebo?

Results: The First 400 Patients with our thanks!

Enrolment: n=342 Eligible Non-Enrolled n (%) No SDM available 157 (46) SDM/patient decline 92 (27) Missed 37 (11) Co-enrolment not pursued 7 (2) Co-enrolment prohibited 11 (3) Language barrier 7 (2) MD decline 13 (4) RC did not approach 1 (0.3) Randomized in a related study 9 (3) Other 8 (2) PROSPECT Consent rate 400/492 = 81.3%

Demographics Group A n=201 Group B n=199 Total n=400 Age, mean (SD)59 (17)62 (16)60 (17) APACHE II, mean (SD)21 (8)22 (8) Females, n (%)86 (43)92 (46)178 (45) Type of Patient, n (%) Medical Surgical Trauma 168 (84) 13 (7) 20 (10) 161 (81) 20 (10) 18 (9) 329 (82) 33 (8) 38 (10) Admitting Diagnosis, n (%) Cardiovascular Respiratory Neurologic Sepsis Trauma 22 (11) 86 (43) 25 (12) 16 (8) 17 (9) 67 (34) 36 (18) 39 (20) 17 (9) 39 (10) 153 (38) 61 (15) 64 (16) 33 (8) Study Day 1 Invasive mechanical ventilation201 (100)199 (100)400 (100) Inotropes or vasopressors108 (54)109 (55)217 (54) Dialysis16 (8)18 (9)34 (9)

Adherence Reason for not receiving study productn=5291 patient-days n (%) Any legitimate reason1108 (21) Randomized late in day (am dose not given)250 (5) Patient discharged from ICU or died262 (5) Consent withdrawn, drug stopped1 (0.02) Strict NPO166 (3) PEG or G-tube insertion42 (1) Feeding tube blocked7 (0.1) No feeding tube available73 (1) Suspected/proven exclusion criterion198 (4) Suspected/proven intestinal ischemia1 (0.02) Patient expected to die, palliative measures75 (1) GI intolerance29 (0.5) Patient vomited dose5 (0.1) Patient declined dose10 (0.2) Other35 (1) Non-adherence (error, missed ≥1 dose)109 (2) Possible missed dose (RN did not sign off)61 (1)

Contamination n=400 patients Open label probiotics ever in ICU0 (0.0) Medically prescribed probiotics within the last 3 days prior to randomization 2 (0.5)

Clinical Outcomes n=400 Patients Death in ICU, n (%)80/398 (20) ICU length of stay median (IQR) n= (7-18) Death in hospital, n (%)108/396 (27) Hospital length of stay median (IQR) n= (13-37) Clostridium difficile infection, n (%) Pre-PROSPECT In ICU, post-PROSPECT randomization Post ICU discharge 4 (1) 9 (2) 8 (2)

Summary PROSPECT is well underway High consent rate Minimal non-adherence No contamination Clinically rich dataset to find out the influence of probiotics on several secondary outcomes as well as VAPs Thank you to all the Research Coordinators and Investigators!

Acknowledgments Drs. Deborah Cook and Maureen Meade, and the Steering Committee (DJC, MM, FL, JCM, LT) Site Investigators Research Coordinators CCCTG Funding agencies Patients & Families