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

Spontaneous Bacterial Peritonitis Clinical Trial

— ASEPTIC  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04395365
• Other study ID #: 17/0894
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 30, 2019
• Est. completion date: October 2025

Study information

• Verified date: November 2023
• Source: University College, London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

See above

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 442
• Est. completion date: October 2025
• Est. primary completion date: October 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Peritonitis
• Spontaneous Bacterial Peritonitis

Intervention

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

Locations

Country	Name	City	State
United Kingdom	Royal Free hospital	Hampstead	London

Sponsors (2)

Lead Sponsor	Collaborator
University College, London	National Institute for Health Research, United Kingdom

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Spontaneous Bacterial peritonitis	Time to first incidence of spontaneous bacterial peritonitis (SBP)	Minimum period of 18 months from randomisation
Secondary	Hospital admissions	Hospital admission rates	Minimum period of 18 months from randomisation
Secondary	C. difficile-associated diarrhoea	Incidence of C. difficile-associated diarrhoea	Minimum period of 18 months from randomisation
Secondary	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
Secondary	Cirrhosis related events	Incidence of other cirrhosis related events (e.g. variceal haemorrhage)	Minimum period of 18 months from randomisation
Secondary	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
Secondary	Anti-microbial resistance	Incidence of anti-microbial resistance	Minimum period of 18 months from randomisation
Secondary	Liver transplantation	Incidence of liver transplantation	Minimum period of 18 months from randomisation
Secondary	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
Secondary	Safety and treatment-related serious adverse events	Safety and treatment-related serious adverse events	Minimum period of 18 months from randomisation
Secondary	Treatment adherence	Treatment adherence (assessed by MARS questionnaire)	Minimum period of 18 months from randomisation
Secondary	Health-related quality of life	Health-related quality of life assessed using EQ-5D-5L questionnaire	Minimum period of 18 months from randomisation
Secondary	Health and social care	Health and social care resource use assessed using Hospital Episode Statistics (HES) database	Minimum period of 18 months from randomisation
Secondary	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
Secondary	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
Secondary	Transjugular intrahepatic portosystemic shunt (TIPS) insertion	Incidence of Transjugular intrahepatic portosystemic shunt (TIPS) insertion	Minimum period of 18 months from randomisation