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Doxycycline for the Prevention of Spontaneous Bacterial Peritonitis

Completed
Conditions
Cirrhosis
Spontaneous Bacterial Peritonitis
Registration Number
NCT04153604
Lead Sponsor
Methodist Health System
Brief Summary

The utilization of doxycycline for SBP prophylaxis is a novel practice at MDMC. Therefore, an assessment of safety and efficacy is needed in order to generalize this practice. The publication of this study can potentially introduce a new alternative to guideline-directed therapies for secondary prevention of SBP. Doxycycline is non-inferior to guideline-directed therapies regarding safety and efficacy in primary and secondary prophylaxis for SBP.

Detailed Description

Spontaneous bacterial peritonitis (SBP) is a common and serious complication in cirrhotic patients with a reported mortality rate of 20 to 30%.1-3 A SBP diagnosis requires abdominal paracentesis and is made in the presence of an elevated ascitic fluid absolute polymorphonuclear leukocyte (PMN) count without an evident intra-abdominal, surgically treatable source of infection.2,3 Common pathogens associated with SBP are Gram-negative colonic organisms. However, in recent years, Gram-positive pathogens have become more common, suggesting the need to evaluate SBP management.1,4-6 The recurrence rate of SBP after an initial episode has been reported to be as high as 70%.1-3 Currently, the American Association for the Study of Liver Disease (AASLD) and European Association for the Study of the Liver (EASL) guidelines recommend the use of sulfamethoxazole/trimethoprim, norfloxacin, or ciprofloxacin for the prevention of recurrent SBP. Fluoroquinolones as a class have had increased black box warnings in recent years, making ciprofloxacin fall out of favor for long-term prophylaxis.5 Sulfamethoxazole/trimethoprim is extensively metabolized by the liver and is contraindicated in marked liver impairment.8 Therefore, it is necessary to search for a prophylaxis alternative with similar efficacy and a better safety profile.

Doxycycline is a broad-spectrum antibiotic that covers Gram-positive bacteria, including Streptococcus spp., resistant strains of Staphylococcus and Enterococcus, and Gram-negative bacteria, including Enterobacteriaceae. One randomized trial in cirrhotic patients with a previous episode of SBP showed that doxycycline was associated with a reduction in inflammatory markers, such as interleukin-6 and C-reactive protein, suggesting potential benefits of doxycycline in this patient population.7 At Methodist Dallas Medical Center (MDMC) and the Liver Institute at MDMC, doxycycline has been utilized for both primary and secondary prevention of SBP. In order to compare doxycycline with guideline-directed therapies for SBP prevention in cirrhotic patients, a retrospective, cohort study was designed to review patients who meet the criteria from July 2014 to July 2018. This study aims to compare the efficacy of doxycycline with that of guideline recommended therapies for primary and secondary SBP prophylaxis, the safety of doxycycline with that of guideline recommended therapies for primary and secondary SBP prophylaxis, and identify the association between chemoprophylaxis and the risk of infections from multidrug resistant organisms (MDROs) in SBP.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
841
Inclusion Criteria
  • Patients ≥ 18 year-old with refractory ascites who are candidates for SBP prophylaxis per clinician's decision
  • Patients diagnosed with cirrhosis based on clinical criteria
  • Patients with a diagnosis of SBP confirmed by paracentesis
Exclusion Criteria
  • Patients who have secondary peritonitis other than SBP
  • Patients who have a history of liver transplant prior to the initial episode of SBP
  • Patients with incomplete medical records

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Occurrence of reported SBPJuly 2014 to July 2018

Occurrence of reported SBP within 1-year of chemoprophylaxis initiation

Secondary Outcome Measures
NameTimeMethod
Hospitalizations and ED visits due to diarrheaJuly 2014 to July 2018

Hospitalizations and ED visits due to diarrhea within 1-year of chemoprophylaxis initiation

Hospitalizations and ED visits due to AKIJuly 2014 to July 2018

Hospitalizations and ED visits due to AKI within 1-year of chemoprophylaxis initiation

Hospitalizations and ED visits due to hyperkalemiaJuly 2014 to July 2018

Hospitalizations and ED visits due to hyperkalemia within 1-year of chemoprophylaxis initiation

Incidences of deathJuly 2014 to July 2018

Incidences of death within 1-year of chemoprophylaxis initiation

Incidences of bacteremiaJuly 2014 to July 2018

Incidences of bacteremia within 1-year of chemoprophylaxis initiation

Rate of infection with MDROJuly 2014 to July 2018

Rate of infection with MDRO within 1-year of chemoprophylaxis initiation

Incidences of Liver transplantJuly 2014 to July 2018

Incidences of liver transplant within 1-year of chemoprophylaxis initiation

Hospitalizations and ED visits due to Clostridioides difficile infectionJuly 2014 to July 2018

Hospitalizations and ED visits due to Clostridioides difficile infection within 1-year of chemoprophylaxis initiation

Trial Locations

Locations (1)

Methodist Dallas Medical Center

🇺🇸

Dallas, Texas, United States

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