Table 2.
Secondary objectives and outcomes
| Secondary objectives and outcome measures | |||
|---|---|---|---|
| # | Objectives | Outcome measures | Time point(s) of evaluation |
| 1 | To compare 14-day all-cause mortality of each regimen | Difference in proportion of those dead in each group | Day 14 |
| 2 | To compare clinical and microbiologic success of each regimen at day 5 |
Difference in proportion of those achieving clinical and microbiological success in each group; defined as: 1. Participant alive 2. Fever resolved (< 38 °C) 3. SOFA score (ICU) or modified SOFA score (non-ICU) improved 4. Absence of growth of index organism |
1. Day 5 2. Day 5 3. Day 1 and day 5 4. Up to and including day 5 |
| 3 | To compare the functional outcome of patients treated with each regimen |
Difference in mean change between baseline and 30-day post-randomisation FBS between groups NB. Baseline reflects pre-admission status prior to condition meriting hospital admission. |
Screening and day 30 |
| 4 | To compare the rates of relapse of bloodstream infection (microbiological failure) with each regimen | Difference in proportion who experience growth of the same organism as index blood culture between groups | Up to Day 30 |
| 5 | To compare the rates of new bloodstream infection with each regimen | Difference in the proportion who experience growth of a new organism from blood cultures (not a contaminant) between groups | Up to Day 30 |
| 6 | To compare lengths of inparticipant hospital (acute) and ICU stay with each regimen [not including inparticipant rehabilitation, long term acute or Hospital in the Home (HITH)] | Difference in median ICU ± non-ICU length of hospital stay between groups | Cumulative up to day 30 |
| 7 | To compare the number of treatment-emergent serious adverse events with each regimen | Difference in proportion of treatment-emergent serious adverse events between groups | Day 1 to the last dose plus 24 h |
| 8 | To compare rates of CDI with each regimen | Difference in proportion of clinician diagnosed (including a positive CDI test) and treated CDI between groups | 30 days |
| 9 | To compare rates of colonisation and/or infection with multi-resistant bacterial organisms (MROs) including those newly acquired |
Difference in proportion of those with MROs identified between groups; defined as: 1. Known previous or current colonisation and/or infection with MRO. 2. MROs detected from any clinical specimen. MROs include vancomycin-resistant Enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA) and multi-resistant gram negative organisms including carbapenem-resistant Enterobacterales (CRE), carbapenemase-producing Enterobacterales (CPE), carbapenem-resistant Pseudomonas aeruginosa (CRP), carbapenem-resistant Acinetobacter baumannii (CRAB) |
Baseline and up to day 30 |
| 10 | To compare the Desirability of Outcome Ranking (DOOR) with partial credit with each regimen |
Mean difference in DOOR between groups at Day 30 post-randomisation. This is based on: 1.Vital status (alive or dead) 2. C. difficile infection 3. CRE colonisation 4. Functional status (i.e. FBS) |
Day 30 |
N.B. A priori, all endpoints will be assessed both for the entire study population and for the study population with bloodstream infection due to (1) E.coli and Klebsiellae spp. or (2) chromosomal AmpC-producer (Enterobacter spp., Klebsiella aerogenes, Citrobacter freundii, Morganella morganii, Providencia spp. or Serratia marcescens)