Primary Antibiotic Prophylaxis Using Co-trimoxazole to Prevent Spontaneous Bacterial Peritonitis in Cirrhosis (ASEPTIC)

A multicentre, interventional, double-blind, placebo-controlled, parallel-arm, phase 3, randomised controlled trial to evaluate the use of co-trimoxazole as primary prophylaxis for spontaneous bacterial peritonitis to improve overall survival

Study Overview

• Status: Active, not recruiting
• Conditions: Spontaneous Bacterial Peritonitis
• Intervention / Treatment: Drug: Placebo oral tablet; Drug: Co-Trimoxazole 960Mg Dispersible Tablet

Detailed Description

See above

• Study Type: Interventional
• Enrollment (Actual): 442
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Trial Manager; Phone Number: 020 3108 4532; Email: ctu.aseptic@ucl.ac.uk
• Study Contact Backup: Name: Marisa Chau; Phone Number: 020 7670 4618; Email: m.chau@ucl.ac.uk

Study Locations

• United Kingdom
  • London
    • Hampstead, London, United Kingdom, NW3 2QG
      • Royal Free Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

1. Patients with Child-Pugh Class B or C cirrhosis and presence of ascites requiring any diuretic treatment or at least 1 or more paracentesis within 3 months prior to enrolment.
2. Patient at least 18 years of age
3. Documented informed consent to participate

Exclusion criteria:

1. Patients with current or previous Spontaneous Bacterial Peritonitis (defined as ascitic polymorphonuclear (PMN) cell count >250/mm3 with either positive or negative ascitic fluid culture without evident intra-abdominal surgically treatable source of infection. A white cell count >500 cell/mm2 or positive microbial culture may be considered as evidence of previous SBP if the site PI considers this was in the context of a likely clinical diagnosis of SBP).
2. Patients receiving palliative care with an expected life expectancy of <8 weeks
3. Allergic to co-trimoxazole, trimethoprim or sulphonamides
4. Pregnant or lactating mothers
5. Patient enrolled in a clinical trial of investigational medicinal products (IMPs) that would impact on their participation in the study
6. Patients with serum potassium (>5.5 mmol/L) related to pre-existing kidney disease which cannot be reduced*
7. Patients receiving antibiotic prophylaxis (except for rifaximin)*
8. Patients with long-term ascites drains*
9. Women of child-bearing potential and males with a partner of child-bearing potential without effective contraception for the duration of trial treatment

10. Patients with pathological blood count changes

    1. Patients with haemoglobin (Hb) <70g/L*
    2. Granulocytopenia defined as absolute neutrophil counts of less than 500 cells per microliter*
    3. Severe thrombocytopenia with a platelet count <30 x109 /L*
11. Patients with severe renal impairment, with eGFR <15 ml/min*
12. Patients with skin conditions: exudative erythema multiform, Stevens-Johnson syndrome, toxic epidermal necrolysis and drug eruption with eosinophilia and systemic symptoms
13. Patients with congenital conditions: congenital glucose-6-Phosphate dehydrogenase deficiency of the erythrocytes, haemoglobin anomalies such as Hb Köln and Hb Zürich
14. Patients with acute porphyria

15. Any clinical condition which the investigator considers would make the patient unsuitable for the trial.

    • It is common for these investigations to change in patients with cirrhosis and long-term ascitic drains may be removed. Patients can be re-screened for eligibility if this occurs.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Co-trimoxazole; Co-trimoxazole, 960mg capsule oral tablet, to be taken daily for 18 months	Drug: Co-Trimoxazole 960Mg Dispersible Tablet; Antibiotic prophylaxis of Spontaneous Bacterial Peritonitis
Placebo Comparator: Placebo; Placebo, 960mg capsule oral tablet, to be taken daily for 18 months	Drug: Placebo oral tablet; Placebo; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall Survival	The maximum possible period of follow up will be 48 months (assuming a recruitment period of 30 months and 18 months treatment period for final patient recruited)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Spontaneous Bacterial peritonitis	Time to first incidence of spontaneous bacterial peritonitis (SBP)	Minimum period of 18 months from randomisation
Hospital admissions	Hospital admission rates	Minimum period of 18 months from randomisation
C. difficile-associated diarrhoea	Incidence of C. difficile-associated diarrhoea	Minimum period of 18 months from randomisation
Infections other than spontaneous bacterial peritonitis with hospital admission	Incidence of infections other than spontaneous bacterial peritonitis with hospital admission.	Minimum period of 18 months from randomisation
Cirrhosis related events	Incidence of other cirrhosis related events (e.g. variceal haemorrhage)	Minimum period of 18 months from randomisation
Renal dysfunction	Incidence of renal dysfunction with creatinine >133 μmol/L (1.5mg/dL) at any point during hospital admission	Minimum period of 18 months from randomisation
Anti-microbial resistance	Incidence of anti-microbial resistance	Minimum period of 18 months from randomisation
Liver transplantation	Incidence of liver transplantation	Minimum period of 18 months from randomisation
Liver disease assessed by increase in MELD score	Progression of liver disease assessed by increase in MELD score between baseline and end of trial follow up.	Minimum period of 18 months from randomisation
Safety and treatment-related serious adverse events	Safety and treatment-related serious adverse events	Minimum period of 18 months from randomisation
Treatment adherence	Treatment adherence (assessed by MARS questionnaire)	Minimum period of 18 months from randomisation
Health-related quality of life	Health-related quality of life assessed using EQ-5D-5L questionnaire	Minimum period of 18 months from randomisation
Health and social care	Health and social care resource use assessed using Hospital Episode Statistics (HES) database	Minimum period of 18 months from randomisation
Mean incremental cost per quality adjusted life year gained (QALY)	Mean incremental cost per quality adjusted life year gained (QALY)	Minimum period of 18 months from randomisation
Incidence of resolution of ascites with diuretic treatment not required for 6 months	Incidence of resolution of ascites with diuretic treatment not required for 6 months	Minimum period of 18 months from randomisation
Transjugular intrahepatic portosystemic shunt (TIPS) insertion	Incidence of Transjugular intrahepatic portosystemic shunt (TIPS) insertion	Minimum period of 18 months from randomisation

Collaborators and Investigators

• Sponsor: University College, London
• Collaborators: National Institute for Health Research, United Kingdom

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2019
• Primary Completion (Estimated): October 1, 2025
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: April 18, 2020
• First Submitted That Met QC Criteria: May 14, 2020
• First Posted (Actual): May 20, 2020

Study Record Updates

• Last Update Posted (Actual): November 18, 2023
• Last Update Submitted That Met QC Criteria: November 17, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Infections; Peritoneal Diseases; Intraabdominal Infections; Peritonitis; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Anti-Infective Agents, Urinary; Trimethoprim, Sulfamethoxazole Drug Combination
• Other Study ID Numbers: 17/0894

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No