Study on Delayed Graft Function Using Paired Kidneys

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01561599
Recruitment Status : Unknown
Verified February 2016 by Angion Biomedica Corp.
Recruitment status was:  Active, not recruiting
First Posted : March 23, 2012
Last Update Posted : February 22, 2016
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Angion Biomedica Corp

Brief Summary:
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 or disease Intervention/treatment Phase
Delayed Graft Function Drug: BB3 Drug: Normal Saline Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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
Study Start Date : August 2011
Estimated Primary Completion Date : February 2016
Estimated Study Completion Date : May 2016

Arm Intervention/treatment
Placebo Comparator: Normal saline
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

Primary Outcome Measures :
  1. creatinine clearance [ Time Frame: 7 days ]
    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 :
  1. Urine production [ Time Frame: 28 days ]
    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.

  2. Creatinine clearance [ Time Frame: 28 days ]
    Calculated creatinine clearance at days 14 and 28

  3. Incidence of delayed graft function [ Time Frame: 7 days ]
    Incidence of delayed graft function (required dialysis due to inadequate renal function during the first 7 days after transplantation).

  4. Number of dialysis sessions [ Time Frame: 28 days ]
    Number of dialysis sessions through day 7, 14, and 28

  5. Mean total daily urine output [ Time Frame: 14 days ]
    Mean total daily urine output through day 14

  6. Daily serum creatinine [ Time Frame: 7 days ]
    Daily serum creatinine at days 1 to 7

  7. Mean serum creatinine [ Time Frame: 28 days ]
    Mean serum creatinine at days 4, 7, 10, 14, and 28

  8. Length of hospitalization following transplantation [ Time Frame: 28 days ]
    Length of hospitalization following transplantation

  9. Follow-up on graft survival and function [ Time Frame: 12 months ]
    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

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria

  1. Subjects must sign the informed consent document prior to performance of any study related procedure including the Screening procedure.
  2. Males and females ≥ 18 years of age.
  3. Had renal transplantation due to end stage disease requiring chronic dialysis.
  4. Study drug can be administered within 6 to 36 hours after transplantation.
  5. Received kidney from donor after cardiac death.
  6. DCD kidney fulfills the clinical site's criteria for transplantation.
  7. Creatinine clearance from the transplanted kidney over a 2-hour collection period is <10 mL/min, OR no urine output OR average urine output of < 50 cc/H over 8 or more consecutive hours,, OR normal urine output following transplantation that diminished to average of < 50 cc/H over 8 or more consecutive hours, OR Creatinine reduction ratio 24 hours after transplantation to pre-transplantation is < 30%.
  8. Dry weight ≤ 100 kg.
  9. Women of child bearing potential have a negative pregnancy test prior to transplantation.
  10. 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.
  11. In the opinion of the Investigator, the subject is capable of understanding and complying with the protocol.

Exclusion Criteria

  1. Mean arterial pressure <40 mmHg or cardiac index <1.8 L/min/m2.
  2. Recipient of multiple organ transplantation or scheduled for multiple organ transplantation.
  3. Recipient of kidney from a pediatric donor age 10 years or less.
  4. Recipient age > 75 years.
  5. Patients with ASA 4 or 5
  6. Patients with chronic obstructive pulmonary disease (COPD) GOLD IV
  7. Has measurable donor-specific antibody or positive cross-match requiring deviation from standard immunosuppressive therapy.
  8. 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.
  9. Concurrent sepsis or active bacterial infection.
  10. Have an active malignancy or history of solid, metastatic or hematologic malignancy with the exception of basal or squamous cell carcinoma of the skin that has been removed.
  11. Women of child bearing potential who is breast feeding.
  12. History of positive HIV test.
  13. History of rheumatoid arthritis.
  14. History of proliferative retinopathy or laser surgery for retinopathy.
  15. Subjects who have a penicillin allergy.
  16. Subjects who require the cytochrome P450 1A2 (CYP1A2) inhibitors, or are receiving ciprofloxacin and fluvoxamine (Luvox®).
  17. Subject is unwilling or unable to comply with the protocol or to cooperate fully with the Investigator or the site personnel.
  18. Subject is not deemed medically stable for the study in the opinion of the Investigator or the subject's primary nephrologist.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01561599

Maastricht University Medical Center
Minderbroedersberg, Maastricht, Netherlands, 6211 LK
Hospital Clínico San Carlos
San Carlos, Madrid, Spain, 28001
United Kingdom
The Newcastle Upon Tyne Hospital
Newcastle, metropolitan county of Tyne and Wear, United Kingdom, NE7 7DN
Sponsors and Collaborators
Angion Biomedica Corp
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Responsible Party: Angion Biomedica Corp Identifier: NCT01561599     History of Changes
Other Study ID Numbers: 004-09
2010-019243-19 ( EudraCT Number )
2R44DK078455-02 ( U.S. NIH Grant/Contract )
First Posted: March 23, 2012    Key Record Dates
Last Update Posted: February 22, 2016
Last Verified: February 2016

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
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action