A Phase 1, Open Label, Non Randomised Safety Trial of Intraperitoneal tPA and DNase in Peritoneal Dialysis Patients With Peritonitis
Trial Snapshot
- Phase
- Phase 1
- Status
- Terminated
- Enrollment
- 5
- Locations
- 1
- Primary Endpoint
- Adverse reactions
Study Overview
Brief Summary
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:
- To examine the tolerability of different doses of intraperitoneal tPA and DNase compared to standard treatment.
- To examine the changes in biochemical and clinical outcomes of PD Peritonitis with the addition of intraperitoneal tPA and DNase to usual therapy.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 100 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
- •Age > 18 years old
Exclusion Criteria
- •More than one organism on culture
- •Contra-indication for systemic thrombolysis (eg. current or recent stroke, major haemorrhage or major trauma; proliferative retinopathy; major surgery in the previous 5 days)
- •Known sensitivity to DNase or t-PA
- •Pregnancy or lactating mother
- •Expected survival less than 3 months
- •Clinical indication for PD catheter removal, as defined by treating team
- •Inability to provide written informed consent
- •Systemic anticoagulation
- •Severe uncontrolled hypertension
- •Documented ulcerative gastrointestinal disease during the last three months
Arms & Interventions
Single dose
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.
Intervention: Tissue Plasminogen Activator (tPA) (Drug)
Single dose
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.
Intervention: recombinant deoxyribonuclease (DNase) (Drug)
2 doses
The next 5 consented participants will be administered t-PA 10mg + DNase 5mg instilled twice a day for one day
Intervention: Tissue Plasminogen Activator (tPA) (Drug)
2 doses
The next 5 consented participants will be administered t-PA 10mg + DNase 5mg instilled twice a day for one day
Intervention: recombinant deoxyribonuclease (DNase) (Drug)
4 doses
The next 5 consented participants will be administered tPA 10mg + DNase 5mg twice a day for 2 days.
Intervention: Tissue Plasminogen Activator (tPA) (Drug)
4 doses
The next 5 consented participants will be administered tPA 10mg + DNase 5mg twice a day for 2 days.
Intervention: recombinant deoxyribonuclease (DNase) (Drug)
Outcomes
Primary Outcomes
Adverse reactions
Time Frame: 72 hours
Participants will be examined for potential adverse reactions during this trial, including - pain; abnormalities in systemic coagulation profile; bleeding; and altered blood pressure.
Secondary Outcomes
- Biochemical markers of inflammation(21 days)
- Clinical markers of inflammation(21 days)
Investigators
Aron Chakera
Dr
Sir Charles Gairdner Hospital