Doxycycline for the Prevention of Spontaneous Bacterial Peritonitis

Cirrhosis Clinical Trial

Official title:

Doxycycline for the Prevention of Spontaneous Bacterial Peritonitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04153604
• Other study ID #: 061.PHA.2019.D
• Status: Completed
• Start date: November 4, 2019
• Est. completion date: August 7, 2020

Study information

• Verified date: March 2024
• Source: Methodist Health System
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 841
• Est. completion date: August 7, 2020
• Est. primary completion date: August 7, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cirrhosis
• Peritonitis
• Spontaneous Bacterial Peritonitis

Intervention

Drug:
• doxycycline
a tetracycline antibiotic that fights bacteria in the body.

Locations

Country	Name	City	State
United States	Methodist Dallas Medical Center	Dallas	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Methodist Health System

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of reported SBP	Occurrence of reported SBP within 1-year of chemoprophylaxis initiation	July 2014 to July 2018
Secondary	Incidences of death	Incidences of death within 1-year of chemoprophylaxis initiation	July 2014 to July 2018
Secondary	Incidences of Liver transplant	Incidences of liver transplant within 1-year of chemoprophylaxis initiation	July 2014 to July 2018
Secondary	Incidences of bacteremia	Incidences of bacteremia within 1-year of chemoprophylaxis initiation	July 2014 to July 2018
Secondary	Hospitalizations and ED visits due to AKI	Hospitalizations and ED visits due to AKI within 1-year of chemoprophylaxis initiation	July 2014 to July 2018
Secondary	Hospitalizations and ED visits due to Clostridioides difficile infection	Hospitalizations and ED visits due to Clostridioides difficile infection within 1-year of chemoprophylaxis initiation	July 2014 to July 2018
Secondary	Hospitalizations and ED visits due to diarrhea	Hospitalizations and ED visits due to diarrhea within 1-year of chemoprophylaxis initiation	July 2014 to July 2018
Secondary	Hospitalizations and ED visits due to hyperkalemia	Hospitalizations and ED visits due to hyperkalemia within 1-year of chemoprophylaxis initiation	July 2014 to July 2018
Secondary	Rate of infection with MDRO	Rate of infection with MDRO within 1-year of chemoprophylaxis initiation	July 2014 to July 2018