the Influence of Prophylactic and Empirical Anti-fungal Treatment in Severe Sepsis Patients With Perforations

Prophylactic Annti-fungal Treatment in Severe Sepsis Patients With Perforations in SICU

This prospective intended to observe the influence of prophylactic and empirical anti-fungal treatment on Severe Sepsis patients with perforations. With the consent of patients' legal guardian for prophylactic use of antifungal agents, patients were divided into two groups: prophylactic group and Empirical group.

Study Overview

• Status: Completed
• Conditions: Intra-abdominal Perforation
• Intervention / Treatment: Drug: fluconazole and caspofungin

Detailed Description

Intra-abdominal perforation is the high risk of fungal infection. The flora in digestive tract would colonize and go to the blood to develop severe bacteria and fungal infection in intra-abdominal perforation and about one-third of patients with gastrointestinal perforations or anastomotic leakages in ICU develop intra-abdominal fungal infection. In particular, the severe sepsis arisen from these infections could further increase the mortality. However, empiric/preemptive treatment in most studies failed to improve the prognosis and few of the studies that addressed the influence of prophylactic anti-fungal treatment in patients with GI Perforation.

• Study Type: Interventional
• Enrollment (Actual): 223
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. age ≥16 years
2. the time between gastrointestinal perforations or anastopmotic leakage(s) after abdominal surgery and entering ICU within 6 hours
3. ICU stay of at least 5 days
4. APACHE Ⅱ score within 24 hours of randomization of 16 or more
5. severe sepsis
6. written informed consent -

Exclusion Criteria:

1. documented fungus before gastrointestinal perforations/anastopmotic leakage(s) ongoing antifungal treatment before the study;
2. fluconazole/caspofungin allergy;
3. pregnant of lactating woman;
4. life expectancy of 48 hours or less. -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prophylactic group; Patients would received intravenous fluconazole (loading dose 800 mg, then 400 mg/day) or caspofungin (loading dose 70 mg, then 50 mg/day) if patients had organ failure or renal or liver dysfunction during the immediately surgery. The antifungal treatment would continue for 5 to 7 days.	Drug: fluconazole and caspofungin
No Intervention: Empirical group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
all cause mortality	six months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
fungal infection	An blood specimen and abdominal drainage fluids if available were obtained for microbiological culture at the time of the gastrointestinal perforations and intra-abdominal specimen was collected at the time of the immediately surgery. All specimens were also obtained 1st, 3rd, 5th, 7th day after perforations and thereafter at 3 days intervals.	six months

Collaborators and Investigators

• Sponsor: Nanjing PLA General Hospital
• Investigators: Principal Investigator: gao tao, ph.d, Nanjing PLA General Hospital; Study Director: cao chun, ph.d, Nanjing PLA General Hospital; Principal Investigator: shi jialiang, ph.d, Nanjing PLA General Hospital

Publications and helpful links

General Publications

• Montravers P, Dupont H, Gauzit R, Veber B, Auboyer C, Blin P, Hennequin C, Martin C. Candida as a risk factor for mortality in peritonitis. Crit Care Med. 2006 Mar;34(3):646-52. doi: 10.1097/01.CCM.0000201889.39443.D2.
• Senn L, Eggimann P, Ksontini R, Pascual A, Demartines N, Bille J, Calandra T, Marchetti O. Caspofungin for prevention of intra-abdominal candidiasis in high-risk surgical patients. Intensive Care Med. 2009 May;35(5):903-8. doi: 10.1007/s00134-009-1405-8. Epub 2009 Jan 27.

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: October 15, 2016
• First Submitted That Met QC Criteria: October 19, 2016
• First Posted (Estimate): October 21, 2016

Study Record Updates

• Last Update Posted (Estimate): October 21, 2016
• Last Update Submitted That Met QC Criteria: October 19, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: fungal infection; severe sepsis; surgical intensive care unit; intra-abdominal perforation; prophylactic anti-fungal treatment
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Caspofungin; Fluconazole
• Other Study ID Numbers: 2012NLY032

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided