Efficacy and Local Tolerability of Topically Applied Heparin on the Suitability of Newly Constructed Primary Arteriovenous Fistulas in Patients Planned for Haemodialysis

This study has been terminated.
(The Sponsor decided to terminate the study due to the low patient recruitment.)
Sponsor:
Information provided by (Responsible Party):
Cyathus Exquirere Pharmaforschungsgmbh
ClinicalTrials.gov Identifier:
NCT01382888
First received: June 24, 2011
Last updated: May 7, 2014
Last verified: May 2014
  Purpose

The primary objective of this study is to evaluate the effect of topically applied heparin in comparison to placebo on suitability of newly constructed primary arteriovenous fistulas in patients planned for haemodialysis at 7th week (± 1 week) after first study drug administration.


Condition Intervention Phase
Haemodialysis
Drug: Heparin 2,400 IU /ml Cutaneous Spray
Drug: Placebo Cutaneous Spray
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Efficacy and Local Tolerability of Topically Applied Heparin (Heparin 2,400 IU /ml Cutaneous Spray) on the Suitability of Newly Constructed Primary Arteriovenous Fistulas in Patients Planned for Haemodialysis. A Multicentre, Randomized, Double-blind and Placebo-controlled Pilot Study

Resource links provided by NLM:


Further study details as provided by Cyathus Exquirere Pharmaforschungsgmbh:

Primary Outcome Measures:
  • Dialysis with a blood flow rate ≥ 300 ml/min OR, if the patient is not in need of dialysis, by combining the venous diameter > 0.4 cm and flow volume > 500ml/min assessed by duplex ultrasound, as well as via clinical impression [ Time Frame: 7 ± 1 week ] [ Designated as safety issue: No ]
    Primary outcome measure is the suitability of the AVF (dialysis with a blood flow rate ≥ 300 ml/min ) at 7th week (± 1 week) after first study drug administration. Suitability of the AVF will be assessed by using the AVF for dialysis. If a flow rate of at least 300 ml/min can be reached for at least 3 minutes suitability is fulfilled.If the patient is not in need of dialysis, suitability will be assessed by combining the venous diameter > 0.4 cm and flow volume > 500ml/min assessed by duplex ultrasound, as well as via clinical impression


Secondary Outcome Measures:
  • Dialysis with a blood flow rate ≥ 300mL/min. If the patient is not in need of dialysis, by combining the venous diameter > 0.4 cm and flow volume > 500ml/min assessed by duplex ultrasound, as well as via clinical impression. [ Time Frame: at 12th and 24th week after first study drug administration ] [ Designated as safety issue: No ]
    The suitability of the AVF (dialysis with a blood flow rate ≥ 300mL/min) at 12th and 24th week after first study drug administration. If a flow rate of at least 300 ml/min can be reached for at least 3 minutes suitability is fulfilled. If the patient is not in need of dialysis, the suitability will be assessed by combining the venous diameter > 0.4 cm and flow volume > 500ml/min assessed by duplex ultrasound, as well as via clinical impression.

  • The functional (unassisted) patency of AVF [ Time Frame: at 7th, 12th and 24th weeks after first study drug administration ] [ Designated as safety issue: No ]
    Unassisted patency of the AVF will be assessed by palpation and auscultation for at least 30 seconds.

  • Local safety and tolerability profile of IMP by patients and investigator (Global assessment of tolerability) [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
    A scale will be used to assess local tolerability. In addition the investigator will screen for known heparin specific reactions, i.e. skin rash and skin swelling.


Enrollment: 30
Study Start Date: July 2011
Study Completion Date: April 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Heparin 2,400 IU /ml Cutaneous Spray
Patients are randomized to receive the active comparator heparin 2,400 IU/ml cutaneous spray for 24 weeks
Drug: Heparin 2,400 IU /ml Cutaneous Spray
Randomization will be performed 2 - 14 days post fistula creation surgery following confirmation that the fistula is patent by physical examination. Patients that are randomized to this study arm, will be asked to administer the study medication twice daily. Patients will get adequate training before first administration.
Placebo Comparator: Placebo Cutaneous Spray
Patients are randomized to receive placebo cutaneous spray for 24 weeks
Drug: Placebo Cutaneous Spray
Randomization will be performed 2 - 14 days post fistula creation surgery following confirmation that the fistula is patent by physical examination. Patients that are randomized to this study arm, will be asked to administer the study medication (placebo) twice daily. Patients will get adequate training before first administration.

Detailed Description:

The clinical dilemma surrounding the maturation and suitability of the AVF in patients undergoing hemodialysis suggests the requirement for a medication that can be added to the standard therapy with in order to help maturation and suitability of newly created AVF. Numerous research papers published over the past 25 years indicate that heparin might have a positive impact on main factors involved in the early failure of native AVF to mature.

In total 56 eligible patients will be enrolled after giving informed consent. Screening will take place in the preceding 6 weeks before scheduled AVF creation. Only patients receiving a Brescia - Cimino (radio - cephalic) fistula or a distal ulnar artery to basilica vein, proximal radial artery to transposed basilica vein, brachial artery to transposed basilica vein and brachial artery to cephalic vein will later be randomized. Patients will be randomly assigned in equal proportions (each group 28 patients) to receive either topically applied heparin (Heparin 2,400 IU /ml Cutaneous Spray) or placebo using a computer-generated randomization. Participants and members of the study team will be blinded to treatment assignment. Patients will be instructed how to use and administer study medication for the consecutive 24 weeks following randomization.

Assessment of the primary endpoint (suitability of newly constructed primary arteriovenous fistulas) is done at 7th week (± 1 week) after first study drug administration. The suitability and unassisted patency and local safety and tolerability by physician and patient of the AVF will also be determined at 12 weeks (± 1 week) and 24 weeks (± 1 week) after first study drug administration. Administration of study medication will be stopped at week 24 after randomization.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and/or female outpatients
  • Aged over 18 years
  • Stage 4 or 5 Chronic kidney Disease according to KDOQI classification
  • Surgery to create an arteriovenous fistula in the lower arm is planned
  • If female of childbearing potential: agree to maintain reliable birth control throughout the study and negative (urine) pregnancy test

Exclusion Criteria:

  • Known hypersensitivity to any component of the study medication
  • History of previous arm (side of planned AVF), neck, or chest surgery/trauma
  • Anticipated kidney transplant from living donor within the next 3 months
  • Presence of any comorbidity that limits patient's life expectancy to less than 6 months.
  • Pregnancy / lactation or intention to fall pregnant during the time course of the study and women of childbearing potential who are not using adequate contraception
  • Known bleeding disorder or established diagnosis of active or suspected bleeding
  • Platelet count less than 80 x 10^9/L
  • Uncontrolled hypertension: Diastolic blood pressure > 115 mm Hg or Systolic blood pressure > 200 mm Hg
  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: NCT01382888

Locations
Austria
Krankenhaus der Elisabethinen Linz
Linz, Austria, 4020
Universitätsklinik für Innere Medizin III, Klinische Abteilung für Nephrologie und Dialyse, Medizinische Universität Wien
Vienna, Austria, 1090
6. Medizinische Abteilung mit Nephrologie und Dialyse, Wilhelminenspital Wien
Vienna, Austria, 1160
Sponsors and Collaborators
Cyathus Exquirere Pharmaforschungsgmbh
  More Information

No publications provided

Responsible Party: Cyathus Exquirere Pharmaforschungsgmbh
ClinicalTrials.gov Identifier: NCT01382888     History of Changes
Other Study ID Numbers: CYT/Heparin - 01/11, 2011-000455-16
Study First Received: June 24, 2011
Last Updated: May 7, 2014
Health Authority: Austria: Agency for Health and Food Safety

Keywords provided by Cyathus Exquirere Pharmaforschungsgmbh:
Haemodialysis
Arteriovenous fistula
Severe chronic kidney disease
Newly constructed primary arteriovenous fistulas in patients planned for haemodialysis

Additional relevant MeSH terms:
Arteriovenous Fistula
Fistula
Arteriovenous Malformations
Vascular Malformations
Cardiovascular Abnormalities
Cardiovascular Diseases
Vascular Fistula
Vascular Diseases
Congenital Abnormalities
Pathological Conditions, Anatomical
Calcium heparin
Heparin
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents

ClinicalTrials.gov processed this record on August 26, 2014