Clinical trial NCT04153604: Doxycycline for the Prevention of Spontaneous Bacterial Peritonitis
Official title: Doxycycline for the Prevention of Spontaneous Bacterial Peritonitis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cirrhosis
Spontaneous Bacterial Peritonitis
Lead sponsor: Methodist Health System
Sponsor class: OTHER
First posted: 2019-11-06
Enrollment: 841
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients hospitalized at MDMC at the Liver Institute Clinic with a diagnosis of SBP based on ascitic fluid PMN count greater than 250 cells/mm3 from July 2014 to July 2018.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Occurrence of reported SBP
timeFrame: July 2014 to July 2018
Secondary outcomes:
measure: Incidences of death
timeFrame: July 2014 to July 2018
measure: Incidences of Liver transplant
timeFrame: July 2014 to July 2018
measure: Incidences of bacteremia
timeFrame: July 2014 to July 2018
measure: Hospitalizations and ED visits due to AKI
timeFrame: July 2014 to July 2018
measure: Hospitalizations and ED visits due to Clostridioides difficile infection
timeFrame: July 2014 to July 2018
measure: Hospitalizations and ED visits due to diarrhea
timeFrame: July 2014 to July 2018
measure: Hospitalizations and ED visits due to hyperkalemia
timeFrame: July 2014 to July 2018
measure: Rate of infection with MDRO
timeFrame: July 2014 to July 2018
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Methodist Dallas Medical Center
state: Texas
Study officials:
affiliation: The Methodist Hospital Research Institute
name: Jessica Rago, PharmD
role: PRINCIPAL_INVESTIGATOR
References: