Three-Chamber Bags Retrospective Study in Spain

This is a retrospective observational database study of patients receiving parenteral nutrition (PN) for at least 3 consecutive days with hospital admission date between January 1, 2013, and December 31, 2015 (study period).

The study will use an as treated approach, where patients will be followed from the index date (hospital admission day of the hospitalization during which PN is administered) up to patient discharge or death (observation period).

The study will be conducted using an initial EMR (Electronic Medical Record) data retrieval process, followed by manual data retrieval (chart review) that will complement data obtained from EMR. Data collection for manual data retrieval will be conducted through an eCRF.

The documentation of patient data will comprise two sequential steps. The initial step will include data of 30% of patients and then an interim analysis (IA) will be conducted. If IA shows positive results, data for the remaining 70% of patients (step II) will be gathered.

The study will be conducted in 10-14 sites in Spain.

Data analysis: Baseline demographics, co-morbidities, and hospitalization characteristics will be reported descriptively by means of mean with standard deviations and medians with ranges for continuous variables and by counts and percentages for categorical variables. Incidence rates for BSI will be reported by treatment group.

Primary outcomes

• Percentage of Patients Presenting With a Confirmed Microbial Blood Stream Infection During Treatment With PN for Each Group (3CB vs HCB) [Entire study period, from January 1, 2013 and December 31, 2015]: Confirmation of BSI required fulfillment of all of the following criteria: * International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code for sepsis (038.x), septicemia (995.91), severe sepsis (995.92), septic shock (785.52), bacteremia (790.7), unspecified infection due to central venous catheter (999.31), or BSI due to central venous catheter (999.32) * Positive blood culture collected during PN administration * Concomitant antimicrobial therapy

Secondary outcomes

• Sepsis During PN [From date of admission to date of discharge]: Percentage of patients presenting at least one episode of Sepsis during treatment with PN for each group (3CB vs HCB)
• Treatment With Antimicrobials During PN [Any day during PN treatment]: Percentage of patients receiving antimicrobial agents during treatment with PN for each group (3CB vs HCB)
• Use of Vasopressor Treatment [Patients requiring vasopressor support at any time during treatment with PN]: Percentages of patients requiring vasopressor support during PN treatment
• Use of Mechanical Ventilation [Patients requiring mechanical ventilation at any time during PN treatment]: Percentage of patients requiring mechanical ventilation during PN treatment for each group (3CB vs HCB)
• Renal Replacement Therapy [Patients requiring renal replacement therapy for at least one day during PN treatment]: Percentage of patients requiring Renal Replacement Therapy during PN treatment for each group (3CB vs HCB)
• Newly-occurred Abnormal Laboratory Findings During PN [During PN treatment inclusive day 1]: Percentage of patients presenting newly-occurred abnormal laboratory results during PN for each group (3CB vs HCB)
• Organ Failure [Any time during PN treatment]: Percentage of patients presenting at least one organ failure during treatment with PN for each group (3CB vs HCB)
• Hospital Length of Stay (LOS) [Duration in days from admission to death or discharge for each treatment arm]: Hospital length of stay in days for patients for each group (3CB vs HCB)
• Length of Stay in the ICU [All patients admitted in the ICU at any time during PN treatment]: Total number of days in the ICU for each group (3CB vs HCB)

Sex: All, ages: 18 Years to any

Inclusion Criteria:

1. Adult hospital inpatients ≥ 18 years
2. Treatment with PN for at least 3 consecutive days
3. PN containing all three major macronutrients, delivered from 3CB or HCB
4. Patients with hospital admission between January 1, 2013, and December 31, 2015 (study period)

Exclusion Criteria:

1. Bloodstream infection before or at the same day of first PN administration
2. Immunosuppression due to concomitant therapy (e.g., immunosuppressive therapy due to transplantation, concomitant oral or intravenous administration of glucocorticoids) or disease (e.g., HIV, leukaemia)
3. Permanent vascular access (port, shunts for dialysis)
4. Femoral venous placement of central venous line used for PN
5. Burns, extensive skin injuries (e.g., Lyell´s disease)
6. Chemo-/radiotherapy for up to 3 months before hospital admission
7. Change of PN bag type during observation period, e.g., from HCBs to 3CBs or vice-versa

Participant flow

Outcome results

• Percentage of Patients Presenting With a Confirmed Microbial Blood Stream Infection During Treatment With PN for Each Group (3CB vs HCB) (Primary), Count of participants, Participants: Three-Chambered Bag 127; Hospital-compounded Bag 106
• Sepsis During PN (Secondary), Count of participants, Participants: Three-Chambered Bag (3CB) 431; Hospital-Compounded Bag (HCB) 228
• Treatment With Antimicrobials During PN (Secondary), Count of participants, Participants: Three-chambered Bag (3CB) 831; Hospital-Compounded Bag (HCB) 370
• Use of Vasopressor Treatment (Secondary), Count of participants, Participants: Three-Chambered Bag (3CB) 410; Hospital-compounded Bag (HCB) 291
• Use of Mechanical Ventilation (Secondary), Count of participants, Participants: Three-Chambered Bag (3CB) 410; Hospital-compounded Bag (HCB) 299
• Renal Replacement Therapy (Secondary), Count of participants, Participants: Three-Chambered Bag (3CB) 78; Hospital-compounded Bag (HCB) 89
• Newly-occurred Abnormal Laboratory Findings During PN (Secondary), Count of participants, Participants: Three-Chambered Bag (3CB) 1193; Hospital-compounded Bag (HCB) 584
• Organ Failure (Secondary), Count of participants, Participants: Three-Chambered Bag (3CB) 905; Hospital-compounded Bag (HCB) 562
• Hospital Length of Stay (LOS) (Secondary), Number, Days: Three-Chambered Bag (3CB) 26,601; Hospital-compounded Bag (HCB) 30,384
• Length of Stay in the ICU (Secondary), Number, Days: Three-Chambered Bag (3CB) 3,017; Hospital-compounded Bag (HCB) 3,772

Adverse events

Time frame: Retrospective, observational, non-interventional study. All-cause mortality, Serious and Other (Not Including Serious) Adverse Events were not monitored/assessed

• Study Protocol and Statistical Analysis Plan (PDF, 2016-05-18)

• John F Stover, Study chair, Fresenius Kabi Deutschland GmbH, Borkenberg 14, 61440 Oberursel, Germany
• Juan Carlos M González, Principal investigator, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain