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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
The University of Western Australia
Information provided by (Responsible Party):
Aron Chakera, Sir Charles Gairdner Hospital
ClinicalTrials.gov Identifier:
NCT01478698
First received: November 21, 2011
Last updated: June 26, 2016
Last verified: June 2016
  Purpose

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.

Condition Intervention Phase
Peritoneal Dialysis
Peritoneal Dialysis, Continuous Ambulatory
Drug: Tissue Plasminogen Activator (tPA)
Drug: recombinant deoxyribonuclease (DNase)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1, Open Label, Non Randomised Safety Trial of Intraperitoneal tPA and DNase in Peritoneal Dialysis Patients With Peritonitis

Resource links provided by NLM:


Further study details as provided by Sir Charles Gairdner Hospital:

Primary Outcome Measures:
  • Adverse reactions [ Time Frame: 72 hours ] [ Designated as safety issue: Yes ]
    Participants will be examined for potential adverse reactions during this trial, including - pain; abnormalities in systemic coagulation profile; bleeding; and altered blood pressure.


Secondary Outcome Measures:
  • Biochemical markers of inflammation [ Time Frame: 21 days ] [ Designated as safety issue: No ]
    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

  • Clinical markers of inflammation [ Time Frame: 21 days ] [ Designated as safety issue: No ]
    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)


Other Outcome Measures:
  • Additional variables [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    gentamycin and vancomycin levels, ultrafiltration volume; mortality; relapse and recurrence rates of peritonitis


Estimated Enrollment: 20
Study Start Date: January 2016
Estimated Study Completion Date: July 2021
Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years to 100 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01478698

Locations
Australia, Western Australia
Sir Charles Gairdner Hospital
Nedland, Western Australia, Australia, 6009
Sponsors and Collaborators
Sir Charles Gairdner Hospital
The University of Western Australia
Investigators
Study Director: Aron Chakera, DPhil Sir Charles Gairdner Hospital
  More Information

Responsible Party: Aron Chakera, Dr, Sir Charles Gairdner Hospital
ClinicalTrials.gov Identifier: NCT01478698     History of Changes
Other Study ID Numbers: tPADNase 1 
Study First Received: November 21, 2011
Last Updated: June 26, 2016
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Sir Charles Gairdner Hospital:
peritoneal dialysis
peritoneal dialysis, continuous ambulatory
peritonitis

Additional relevant MeSH terms:
Peritonitis
Intraabdominal Infections
Infection
Peritoneal Diseases
Digestive System Diseases
Plasminogen
Tissue Plasminogen Activator
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 25, 2016