The Safety and Tolerability of Intra-abdominal t-PA and DNase on Peritonitis in Peritoneal Dialysis Patients

Sir Charles Gairdner Hospital

Status and phase: Terminated; Phase 1

Conditions: Peritoneal Dialysis, Continuous Ambulatory; Peritoneal Dialysis

Treatments: Drug: Tissue Plasminogen Activator (tPA); Drug: recombinant deoxyribonuclease (DNase)

Study type: Interventional

Funder types: Other

Identifiers

NCT01478698

tPADNase 1

Details and patient eligibility

About

Hypothesis:

Intraperitoneal tPA and DNase is well tolerated at a number of different doses. Different doses of tPA and DNase will have a dose-related effect on inflammatory markers (CRP and intraperitoneal white cell count).

Aims:

1. To examine the tolerability of different doses of intraperitoneal tPA and DNase compared to standard treatment.
2. To examine the changes in biochemical and clinical outcomes of PD Peritonitis with the addition of intraperitoneal tPA and DNase to usual therapy.

Enrollment: 5 patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. PD patient
2. Proven peritonitis (as defined as at least 2 of: (i) Symptoms and/or signs of peritonitis; (ii) Cloudy dialysate OR dialysate white cell count > 100x 106/L with >50% neutrophils; (iii) Positive culture of dialysate
3. Age > 18 years old

Exclusion criteria

1. More than one organism on culture
2. Contra-indication for systemic thrombolysis (eg. current or recent stroke, major haemorrhage or major trauma; proliferative retinopathy; major surgery in the previous 5 days)
3. Known sensitivity to DNase or t-PA
4. Pregnancy or lactating mother
5. Expected survival less than 3 months
6. Clinical indication for PD catheter removal, as defined by treating team
7. Inability to provide written informed consent
8. Systemic anticoagulation
9. Severe uncontrolled hypertension
10. Documented ulcerative gastrointestinal disease during the last three months

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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5 participants in 4 patient groups

Single dose

Experimental group

Description:

The first 5 consented participants will be administered t-PA 10mg + DNase 5mg instilled into a dialysate bag and infused for a 4 hour intraperitoneal dwell.

Treatment:

Drug: Tissue Plasminogen Activator (tPA)

Drug: recombinant deoxyribonuclease (DNase)

2 doses

Experimental group

Description:

The next 5 consented participants will be administered t-PA 10mg + DNase 5mg instilled twice a day for one day

Treatment:

Drug: Tissue Plasminogen Activator (tPA)

Drug: recombinant deoxyribonuclease (DNase)

4 doses

Experimental group

Description:

The next 5 consented participants will be administered tPA 10mg + DNase 5mg twice a day for 2 days.

Treatment:

Drug: Tissue Plasminogen Activator (tPA)

Drug: recombinant deoxyribonuclease (DNase)

control

No Intervention group

Description:

Any potential participants that have not consented into the intervention arms will be approached to be consented into a non-intervention observational control group. A maximum of 5 participants will be recruited into this control group.