Study on Delayed Graft Function Using Paired Kidneys

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2013 by Angion Biomedica Corp
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Angion Biomedica Corp
ClinicalTrials.gov Identifier:
NCT01561599
First received: March 21, 2012
Last updated: May 21, 2013
Last verified: May 2013
  Purpose

The study is designed to evaluate the safety and efficacy of an intravenously administered drug in recipients of kidneys from cardiac death donors who are risk for developing delayed graft function.


Condition Intervention Phase
Delayed Graft Function
Drug: BB3
Drug: Normal Saline
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Pilot Study of BB3 to Improve Renal Function in Patients With Signs and Symptoms of Significant Renal Injury After Kidney Transplantation From Donors After Cardiac Death

Resource links provided by NLM:


Further study details as provided by Angion Biomedica Corp:

Primary Outcome Measures:
  • creatinine clearance [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    The primary analysis to assess the activity of BB3 compared to placebo will be the mean difference in creatinine clearance over time using selective 24-hour urine collections from the transplanted kidney from the first infusion of study drug through day 7 post-transplant.


Secondary Outcome Measures:
  • Urine production [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Median time (days) until production of ≥1 litre urine over a 24-hour period, i.e. median number of days following the first infusion of study drug until the first day (08:00 - 08:00) that urine production was ≥1 litre over a 24-hour period.

  • Creatinine clearance [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Calculated creatinine clearance at days 14 and 28

  • Incidence of delayed graft function [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    Incidence of delayed graft function (required dialysis due to inadequate renal function during the first 7 days after transplantation).

  • Number of dialysis sessions [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Number of dialysis sessions through day 7, 14, and 28

  • Mean total daily urine output [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    Mean total daily urine output through day 14

  • Daily serum creatinine [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    Daily serum creatinine at days 1 to 7 and at days 1 to 14

  • Mean serum creatinine [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Mean serum creatinine at days 4, 7, 10, 14, and 28

  • Length of hospitalization following transplantation [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Length of hospitalization following transplantation

  • Follow-up on graft survival and function [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Results of the 6- and 12-month follow-up on graft survival and function will be summarized as an addendum to the final clinical study report

  • adverse and serious adverse events, and acute rejection [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    number of adverse and serious adverse events, and number of acute rejection periods


Estimated Enrollment: 36
Study Start Date: August 2011
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Normal saline
Placebo
Drug: Normal Saline
Daily intravenous administration for four (4) days. The volume of normal saline will vary by estimated weight.
Active Comparator: BB3
Small molecule mimetic of hepatocyte growth factor/scatter factor
Drug: BB3
Daily intravenous administration of 2mg/kg for 4 days

Detailed Description:

Renal transplantation is the most effective and cost-efficient form of renal replacement therapy for a burgeoning population that presents with end-stage renal disease. Although organ donation has become a national priority, the gap between the number of patients awaiting a kidney versus the number of available kidneys continues to widen exponentially. In many countries within the European Union, utilization of "donation after cardiac death" (DCD) kidneys is steadily increasing, expanding the donor pool by > 50%. Given the high incidence of cardiac deaths in the US, aggressive pursuit of the DCD kidney pool could potentially reduce waitlist periods to months, if not days. Risk for delayed graft function (DGF) with the attendant risks for increased recipient morbidity, chronic allograft nephropathy and increased medical costs has however tempered DCD kidney utilization in this country. Development of strategies that limit normothermic reperfusion injury, promote renal repair, reduce the incidence and/or duration of DGF and improve long-term outcome can greatly enhance acceptance and recruitment of DCD kidneys. The study is designed to evaluate the safety and efficacy of an intravenously administered drug in recipients of kidneys from DCD donors who are risk for developing DGF. This trial is unique in that it compares drug versus placebo outcome in kidney recipients from the same donor with direct evaluation of function (creatinine clearance) in the graft.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects must sign the informed consent document prior to performance of any study related procedure including the Screening procedure.
  • Males and females ≥ 18 years of age.
  • Had renal transplantation due to end stage disease requiring chronic dialysis.
  • Study drug can be administered within 6 to 36 hours after transplantation.
  • Received kidney from donor after cardiac death.
  • DCD kidney fulfills the clinical site's criteria for transplantation.
  • Creatinine clearance from the transplanted kidney over a 2-hour collection period is <10 mL/min, OR no urine output or < 50 cc/H over a 24 hour period, OR normal urine output following transplantation that diminished to < 50 cc/H over a 24 hour period OR Creatinine reduction ratio 24 hours after transplantation to pre-transplantation is < 30%.• Dry weight ≤ 100 kg.
  • Women of child bearing potential have a negative serum pregnancy test prior to transplantation.
  • Women of child bearing potential (including perimenopausal women who have had a menstrual period within 1 year) must agree to use 2 forms of effective birth control regimen (at least one-barrier method) during the 28-day study period. Men must agree to use condoms during the study period; a condom with spermicide is considered a single barrier.
  • In the opinion of the Investigator, the subject is capable of understanding and complying with the protocol.

Exclusion Criteria:

  • Mean arterial pressure < 40 mmHg or cardiac index < 1.8 L/min/m2.
  • Requires emergency dialysis for reasons other than high plasma creatinine levels, e.g. severe fluid overload or severe metabolic abnormalities.
  • Recipient of multiple organ transplantation or scheduled for multiple organ transplantation.
  • Recipient of kidney from a paediatric donor age 10 years or less.
  • Recipient age > 75 years.
  • Patients with ASA 4 or 5
  • Patients with chronic obstructive pulmonary disease (COPD) GOLD IV
  • Has measurable donor-specific antibody or positive cross-match requiring deviation from standard immunosuppressive therapy.
  • Currently participating in or has participated in an investigational drug or medical device study within 30 days or five half-lives, whichever is longer, prior to enrolment into this study.
  • Concurrent sepsis or active bacterial infection.
  • Have an active malignancy or history of solid, metastatic or haematologic malignancy with the exception of basal or squamous cell carcinoma of the skin that has been removed.
  • Women of child bearing potential who is breast feeding.
  • History of positive HIV test.
  • History of rheumatoid arthritis.
  • History of proliferative retinopathy or laser surgery for retinopathy.
  • Subjects who have a penicillin allergy.
  • Subjects who require the cytochrome P450 1A2 (CYP1A2) inhibitors, or are receiving ciprofloxacin and fluvoxamine (Luvox®).
  • Subject is unwilling or unable to comply with the protocol or to cooperate fully with the Investigator or the site personnel.
  • Subject is not deemed medically stable for the study in the opinion of the Investigator or the subject's primary nephrologist.
  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: NCT01561599

Locations
Netherlands
Maastricht University Medical Centre Recruiting
Maastricht, Netherlands, 6202 AZ
Contact: Tim C van Smaalen, M.D.    +31 43 3875938    tim.van.smaalen@mumc.nl   
Principal Investigator: L. W. Ernest van Heurn, M.D., Ph.D.         
Sub-Investigator: M.H.L. Christiaans, M.D.         
United Kingdom
The Freeman Hospital Recruiting
High Heaton, Newcastle upon Tyne, United Kingdom, NE7 7DN
Contact: Mark Playford, RN    +44191 21 39152    Mark.Playford@nuth.nhs.uk   
Principal Investigator: David Talbot, MBBS MD FRCS PhD         
Sponsors and Collaborators
Angion Biomedica Corp
  More Information

No publications provided

Responsible Party: Angion Biomedica Corp
ClinicalTrials.gov Identifier: NCT01561599     History of Changes
Other Study ID Numbers: 004-09, 2010-019243-19, 2R44DK078455-02
Study First Received: March 21, 2012
Last Updated: May 21, 2013
Health Authority: Netherlands: Medicines Evaluation Board (MEB)
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
United States: Federal Government

Keywords provided by Angion Biomedica Corp:
hepatocyte growth factor mimetic
hepatocyte growth factor(HGF)
Delayed Graft Function (DGF)
Kidney transplantation

Additional relevant MeSH terms:
Delayed Graft Function
Pathologic Processes
Mitogens
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 29, 2014