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

University College London (UCL)

Status and phase: Active, not recruiting; Phase 3

Conditions: Spontaneous Bacterial Peritonitis

Treatments: Drug: Placebo oral tablet; Drug: Co-Trimoxazole 960Mg Dispersible Tablet

Study type: Interventional

Funder types: Other

Identifiers

NCT04395365

17/0894

Details and patient eligibility

About

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

Full description

See above

Enrollment: 442 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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442 participants in 2 patient groups, including a placebo group

Co-trimoxazole

Experimental group

Description:

Co-trimoxazole, 960mg capsule oral tablet, to be taken daily for 18 months

Treatment:

Drug: Co-Trimoxazole 960Mg Dispersible Tablet

Placebo

Placebo Comparator group

Description:

Placebo, 960mg capsule oral tablet, to be taken daily for 18 months

Treatment:

Drug: Placebo oral tablet