ASEPTIC: Primary Antibiotic Prophylaxis Using Co-trimoxazole to Prevent Spontaneous Bacterial Peritonitis in Cirrhosis
Study Details
Study Description
Brief 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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
See above
Study Design
Arms and Interventions
| 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:
|
Outcome Measures
Primary Outcome Measures
- 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)]
Overall Survival
Secondary Outcome Measures
- Spontaneous Bacterial peritonitis [Minimum period of 18 months from randomisation]
Time to first incidence of spontaneous bacterial peritonitis (SBP)
- Hospital admissions [Minimum period of 18 months from randomisation]
Hospital admission rates
- C. difficile-associated diarrhoea [Minimum period of 18 months from randomisation]
Incidence of C. difficile-associated diarrhoea
- Infections other than spontaneous bacterial peritonitis with hospital admission [Minimum period of 18 months from randomisation]
Incidence of infections other than spontaneous bacterial peritonitis with hospital admission.
- Cirrhosis related events [Minimum period of 18 months from randomisation]
Incidence of other cirrhosis related events (e.g. variceal haemorrhage)
- Renal dysfunction [Minimum period of 18 months from randomisation]
Incidence of renal dysfunction with creatinine >133 μmol/L (1.5mg/dL) at any point during hospital admission
- Anti-microbial resistance [Minimum period of 18 months from randomisation]
Incidence of anti-microbial resistance
- Liver transplantation [Minimum period of 18 months from randomisation]
Incidence of liver transplantation
- Liver disease assessed by increase in MELD score [Minimum period of 18 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 serious adverse events [Minimum period of 18 months from randomisation]
Safety and treatment-related serious adverse events
- Treatment adherence [Minimum period of 18 months from randomisation]
Treatment adherence (assessed by MARS questionnaire)
- Health-related quality of life [Minimum period of 18 months from randomisation]
Health-related quality of life assessed using EQ-5D-5L questionnaire
- Health and social care [Minimum period of 18 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) [Minimum period of 18 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 [Minimum period of 18 months from randomisation]
Incidence of resolution of ascites with diuretic treatment not required for 6 months
- Transjugular intrahepatic portosystemic shunt (TIPS) insertion [Minimum period of 18 months from randomisation]
Incidence of Transjugular intrahepatic portosystemic shunt (TIPS) insertion
Eligibility Criteria
Criteria
Inclusion criteria:
-
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.
-
Patient at least 18 years of age
-
Documented informed consent to participate
Exclusion criteria:
-
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).
-
Patients receiving palliative care with an expected life expectancy of <8 weeks
-
Allergic to co-trimoxazole, trimethoprim or sulphonamides
-
Pregnant or lactating mothers
-
Patient enrolled in a clinical trial of investigational medicinal products (IMPs) that would impact on their participation in the study
-
Patients with serum potassium (>5.5 mmol/L) related to pre-existing kidney disease which cannot be reduced*
-
Patients receiving antibiotic prophylaxis (except for rifaximin)*
-
Patients with long-term ascites drains*
-
Women of child-bearing potential and males with a partner of child-bearing potential without effective contraception for the duration of trial treatment
-
Patients with pathological blood count changes
-
Patients with haemoglobin (Hb) <70g/L*
-
Granulocytopenia defined as absolute neutrophil counts of less than 500 cells per microliter*
-
Severe thrombocytopenia with a platelet count <30 x109 /L*
-
Patients with severe renal impairment, with eGFR <15 ml/min*
-
Patients with skin conditions: exudative erythema multiform, Stevens-Johnson syndrome, toxic epidermal necrolysis and drug eruption with eosinophilia and systemic symptoms
-
Patients with congenital conditions: congenital glucose-6-Phosphate dehydrogenase deficiency of the erythrocytes, haemoglobin anomalies such as Hb Köln and Hb Zürich
-
Patients with acute porphyria
-
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Royal Free hospital | Hampstead | London | United Kingdom | NW3 2QG |
Sponsors and Collaborators
- University College, London
- National Institute for Health Research, United Kingdom
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 17/0894