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

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.

Official Title
-----------------
A Phase 1, Open Label, Non Randomised Safety Trial of Intraperitoneal tPA and DNase in Peritoneal Dialysis Patients With Peritonitis

Conditions
-----------------
Peritoneal Dialysis, Peritoneal Dialysis, Continuous Ambulatory

Intervention / Treatment
-----------------
* Drug: Tissue Plasminogen Activator (tPA)
* Drug: recombinant deoxyribonuclease (DNase)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: PD patient 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single dose<br>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. | Drug: Tissue Plasminogen Activator (tPA)<br>* tPA 10mg per dose intraperitoneal<br>Drug: recombinant deoxyribonuclease (DNase)<br>* DNase 5mg per dose given intraperitoneally.<br>|
| Experimental: 2 doses<br>The next 5 consented participants will be administered t-PA 10mg + DNase 5mg instilled twice a day for one day | Drug: Tissue Plasminogen Activator (tPA)<br>* tPA 10mg per dose intraperitoneal<br>Drug: recombinant deoxyribonuclease (DNase)<br>* DNase 5mg per dose given intraperitoneally.<br>|
| Experimental: 4 doses<br>The next 5 consented participants will be administered tPA 10mg + DNase 5mg twice a day for 2 days. | Drug: Tissue Plasminogen Activator (tPA)<br>* tPA 10mg per dose intraperitoneal<br>Drug: recombinant deoxyribonuclease (DNase)<br>* DNase 5mg per dose given intraperitoneally.<br>|
| No Intervention: control<br>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. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse reactions | Participants will be examined for potential adverse reactions during this trial, including - pain; abnormalities in systemic coagulation profile; bleeding; and altered blood pressure. | 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biochemical markers of inflammation | Biochemical markers of inflammation will be measured on days 1, 3, 5, 7, 14 and 21, including - c-reactive protein, white cell count, dialysate white cell count, procalcitonin | 21 days | 
| Clinical markers of inflammation | pain score; days till pain free; proportion requiring catheter removal; days of hospitalisation; days of fever (temperature > 37.0 degrees on at least one occasion) | 21 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
peritoneal dialysis, peritoneal dialysis, continuous ambulatory, peritonitis