Spontaneous Bacterial Peritonitis
Conditions
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
Detailed description
See above
Interventions
DRUGCo-Trimoxazole 960Mg Dispersible Tablet
Antibiotic prophylaxis of Spontaneous Bacterial Peritonitis
DRUGPlacebo oral tablet
Placebo
Sponsors
National Institute for Health Research, United Kingdom
University College, London
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Spontaneous Bacterial peritonitis | Minimum period of 18 months from randomisation | Time to first incidence of spontaneous bacterial peritonitis (SBP) |
| 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 |
| 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. |
Countries
United Kingdom
Outcome results
None listed