Clinical trial NCT04395365: Primary Antibiotic Prophylaxis Using Co-trimoxazole to Prevent Spontaneous Bacterial Peritonitis in Cirrhosis
Official title: Primary Antibiotic Prophylaxis Using Co-trimoxazole to Prevent Spontaneous Bacterial Peritonitis in Cirrhosis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Spontaneous Bacterial Peritonitis
Lead sponsor: University College, London
Sponsor class: OTHER
Collaborators: name: National Institute for Health Research, United Kingdom
First posted: 2020-05-20
Enrollment: 442
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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

Eligibility criteria: 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.

Primary outcomes:
measure: Overall Survival
timeFrame: 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 outcomes:
measure: Spontaneous Bacterial peritonitis
timeFrame: Minimum period of 18 months from randomisation
measure: Hospital admissions
timeFrame: Minimum period of 18 months from randomisation
measure: C. difficile-associated diarrhoea
timeFrame: Minimum period of 18 months from randomisation
measure: Infections other than spontaneous bacterial peritonitis with hospital admission
timeFrame: Minimum period of 18 months from randomisation
measure: Cirrhosis related events
timeFrame: Minimum period of 18 months from randomisation
measure: Renal dysfunction
timeFrame: Minimum period of 18 months from randomisation
measure: Anti-microbial resistance
timeFrame: Minimum period of 18 months from randomisation
measure: Liver transplantation
timeFrame: Minimum period of 18 months from randomisation
measure: Liver disease assessed by increase in MELD score
timeFrame: Minimum period of 18 months from randomisation
measure: Safety and treatment-related serious adverse events
timeFrame: Minimum period of 18 months from randomisation
measure: Treatment adherence
timeFrame: Minimum period of 18 months from randomisation
measure: Health-related quality of life
timeFrame: Minimum period of 18 months from randomisation
measure: Health and social care
timeFrame: Minimum period of 18 months from randomisation
measure: Mean incremental cost per quality adjusted life year gained (QALY)
timeFrame: Minimum period of 18 months from randomisation
measure: Incidence of resolution of ascites with diuretic treatment not required for 6 months
timeFrame: Minimum period of 18 months from randomisation
measure: Transjugular intrahepatic portosystemic shunt (TIPS) insertion
timeFrame: Minimum period of 18 months from randomisation
Other outcomes:
Locations:
city: Hampstead
country: United Kingdom
facility: Royal Free hospital
state: London
Study officials:
References: