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

Overview

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

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Prevention
    • Masking: Triple (Participant, Care Provider, Investigator)
  • Study Primary Completion Date: June 2023

Interventions

  • Drug: Co-Trimoxazole 960Mg Dispersible Tablet
    • Antibiotic prophylaxis of Spontaneous Bacterial Peritonitis
  • Drug: Placebo oral tablet
    • Placebo

Arms, Groups and Cohorts

  • Experimental: Co-trimoxazole
    • Co-trimoxazole, 960mg capsule oral tablet, to be taken daily for 24 months
  • Placebo Comparator: Placebo
    • Placebo, 960mg capsule oral tablet, to be taken daily for 24 months

Clinical Trial Outcome Measures

Primary Measures

  • Spontaneous bacterial peritonitis
    • Time Frame: 24 months following randomisation
    • Time to first incidence of spontaneous bacterial peritonitis

Secondary Measures

  • Mortality
    • Time Frame: Up to 24 months from randomisation
    • All-cause mortality
  • Incidence of spontaneous bacterial peritonitis infection
    • Time Frame: Up to 24 months from randomisation
    • Incidence of spontaneous bacterial peritonitis infection
  • Hospital admissions
    • Time Frame: Up to 24 months from randomisation
    • Hospital admission rates
  • C. difficile-associated diarrhoea
    • Time Frame: Up to 24 months from randomisation
    • Incidence of C. difficile-associated diarrhoea
  • Infections other than spontaneous bacterial peritonitis with hospital admission
    • Time Frame: Up to 24 months from randomisation
    • Incidence of infections other than spontaneous bacterial peritonitis with hospital admission.
  • Renal dysfunction
    • Time Frame: Up to 24 months from randomisation
    • Incidence of renal dysfunction with creatinine >133 μmol/L (1.5mg/dL) at any point during hospital admission
  • Liver transplantation
    • Time Frame: Up to 24 months from randomisation
    • Incidence of liver transplantation
  • Liver disease assessed by increase in MELD score
    • Time Frame: Up to 24 months from randomisation
    • Progression of liver disease assessed by increase in MELD score between baseline and end of trial follow up.
  • Safety and treatment-related adverse events
    • Time Frame: Up to 24 months from randomisation
    • Safety and treatment-related adverse events
  • Treatment adherence
    • Time Frame: Up to 24 months from randomisation
    • Treatment adherence (assessed by MARS questionnaire)
  • Health-related quality of life
    • Time Frame: Up to 24 months from randomisation
    • Health-related quality of life assessed using EQ-5D-5L questionnaire
  • Health and social care
    • Time Frame: Up to 24 months from randomisation
    • Health and social care resource use assessed using Hospital Episode Statistics (HES) database
  • Mean incremental cost per quality adjusted life year gained (QALY)
    • Time Frame: Up to 24 months from randomisation
    • Mean incremental cost per quality adjusted life year gained (QALY)
  • Incidence of resolution of ascites with diuretic treatment not required for 6 months
    • Time Frame: Up to 24 months from randomisation
    • Incidence of resolution of ascites with diuretic treatment not required for 6 months

Participating in This Clinical Trial

Inclusion Criteria

1. Patients with liver cirrhosis and ascites with ascitic fluid protein count <2.0 g/dL (from sample taken within <12 weeks prior to randomisation)

2. Patients with ascitic polymorphonuclear count <250 cells/mm3 and negative microbial culture at 5 days (on the last sample sent within <12 weeks prior to randomisation)

3. Patient at least 18 years of age

4. Documented informed consent to participate

Exclusion Criteria

1. Patients with previous Spontaneous Bacterial Peritonitis (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 persistent hyperkalaemia (>6.5 mmol/L) related to pre-existing kidney disease with reduction not possible

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 (granulocytopenia, megaloblastic anaemia)

11. Severe thrombocytopenia with a platelet count <30 x109 /L

12. Patients with severe renal impairment, with eGFR <15 ml/min

13. Patients with skin conditions: exudative erythema multiform, Stevens-Johnson syndrome, toxic epidermal necrolysis and drug eruption with eosinophilia and systemic symptoms

14. Patients with congenital conditions: congenital glucose-6-Phosphate dehydrogenase deficiency of the erythrocytes, haemoglobin anomalies such as Hb Köln and Hb Zürich

15. Patients with acute porphyria

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University College, London
  • Collaborator
    • National Institute for Health Research, United Kingdom
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Contact(s)
    • David Gear, 02076705748, david.gear.16@ucl.ac.uk

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