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

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

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.

Study Overview

• Status: Terminated
• Conditions: Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory
• Intervention / Treatment: Drug: Tissue Plasminogen Activator (tPA); Drug: recombinant deoxyribonuclease (DNase)

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Western Australia
    • Perth, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 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.	Drug: Tissue Plasminogen Activator (tPA); tPA 10mg per dose intraperitoneal; Drug: recombinant deoxyribonuclease (DNase); DNase 5mg per dose given intraperitoneally.
EXPERIMENTAL: 2 doses; 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); tPA 10mg per dose intraperitoneal; Drug: recombinant deoxyribonuclease (DNase); DNase 5mg per dose given intraperitoneally.
EXPERIMENTAL: 4 doses; The next 5 consented participants will be administered tPA 10mg + DNase 5mg twice a day for 2 days.	Drug: Tissue Plasminogen Activator (tPA); tPA 10mg per dose intraperitoneal; Drug: recombinant deoxyribonuclease (DNase); DNase 5mg per dose given intraperitoneally.
NO_INTERVENTION: control; 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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Additional variables	gentamycin and vancomycin levels, ultrafiltration volume; mortality; relapse and recurrence rates of peritonitis	3 months

Collaborators and Investigators

• Sponsor: Sir Charles Gairdner Hospital
• Collaborators: The University of Western Australia
• Investigators: Study Director: Aron Chakera, DPhil, Sir Charles Gairdner Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2016
• Primary Completion (ACTUAL): May 13, 2022
• Study Completion (ACTUAL): May 13, 2022

Study Registration Dates

• First Submitted: November 21, 2011
• First Submitted That Met QC Criteria: November 22, 2011
• First Posted (ESTIMATE): November 23, 2011

Study Record Updates

• Last Update Posted (ACTUAL): May 19, 2022
• Last Update Submitted That Met QC Criteria: May 12, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: peritoneal dialysis; peritonitis; peritoneal dialysis, continuous ambulatory
• Additional Relevant MeSH Terms: Digestive System Diseases; Infections; Peritoneal Diseases; Intraabdominal Infections; Peritonitis; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Tissue Plasminogen Activator; Plasminogen
• Other Study ID Numbers: tPADNase 1