Study on Delayed Graft Function Using Paired Kidneys
Primary Purpose
Delayed Graft Function
Status
Unknown status
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
BB3
Normal Saline
Sponsored by
About this trial
This is an interventional treatment trial for Delayed Graft Function focused on measuring hepatocyte growth factor mimetic, hepatocyte growth factor(HGF), Delayed Graft Function (DGF), Kidney transplantation
Eligibility 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 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%.
- Dry weight ≤ 100 kg.
- Women of child bearing potential have a negative 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.
- Recipient of multiple organ transplantation or scheduled for multiple organ transplantation.
- Recipient of kidney from a pediatric 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 hematologic 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.
Sites / Locations
- Maastricht University Medical Center
- Hospital Clínico San Carlos
- The Newcastle Upon Tyne Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Active Comparator
Arm Label
Normal saline
BB3
Arm Description
Placebo
Small molecule mimetic of hepatocyte growth factor/scatter factor
Outcomes
Primary Outcome Measures
creatinine clearance
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
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
Calculated creatinine clearance at days 14 and 28
Incidence of delayed graft function
Incidence of delayed graft function (required dialysis due to inadequate renal function during the first 7 days after transplantation).
Number of dialysis sessions
Number of dialysis sessions through day 7, 14, and 28
Mean total daily urine output
Mean total daily urine output through day 14
Daily serum creatinine
Daily serum creatinine at days 1 to 7
Mean serum creatinine
Mean serum creatinine at days 4, 7, 10, 14, and 28
Length of hospitalization following transplantation
Length of hospitalization following transplantation
Follow-up on graft survival and function
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
Full Information
NCT ID
NCT01561599
First Posted
March 21, 2012
Last Updated
February 18, 2016
Sponsor
Angion Biomedica Corp
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
1. Study Identification
Unique Protocol Identification Number
NCT01561599
Brief Title
Study on Delayed Graft Function Using Paired Kidneys
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 Type
Interventional
2. Study Status
Record Verification Date
February 2016
Overall Recruitment Status
Unknown status
Study Start Date
August 2011 (undefined)
Primary Completion Date
February 2016 (Anticipated)
Study Completion Date
May 2016 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Angion Biomedica Corp
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Delayed Graft Function
Keywords
hepatocyte growth factor mimetic, hepatocyte growth factor(HGF), Delayed Graft Function (DGF), Kidney transplantation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Normal saline
Arm Type
Placebo Comparator
Arm Description
Placebo
Arm Title
BB3
Arm Type
Active Comparator
Arm Description
Small molecule mimetic of hepatocyte growth factor/scatter factor
Intervention Type
Drug
Intervention Name(s)
BB3
Intervention Description
Daily intravenous administration of 2mg/kg for 4 days
Intervention Type
Drug
Intervention Name(s)
Normal Saline
Intervention Description
Daily intravenous administration for four (4) days. The volume of normal saline will vary by estimated weight.
Primary Outcome Measure Information:
Title
creatinine clearance
Description
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.
Time Frame
7 days
Secondary Outcome Measure Information:
Title
Urine production
Description
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.
Time Frame
28 days
Title
Creatinine clearance
Description
Calculated creatinine clearance at days 14 and 28
Time Frame
28 days
Title
Incidence of delayed graft function
Description
Incidence of delayed graft function (required dialysis due to inadequate renal function during the first 7 days after transplantation).
Time Frame
7 days
Title
Number of dialysis sessions
Description
Number of dialysis sessions through day 7, 14, and 28
Time Frame
28 days
Title
Mean total daily urine output
Description
Mean total daily urine output through day 14
Time Frame
14 days
Title
Daily serum creatinine
Description
Daily serum creatinine at days 1 to 7
Time Frame
7 days
Title
Mean serum creatinine
Description
Mean serum creatinine at days 4, 7, 10, 14, and 28
Time Frame
28 days
Title
Length of hospitalization following transplantation
Description
Length of hospitalization following transplantation
Time Frame
28 days
Title
Follow-up on graft survival and function
Description
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
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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 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%.
Dry weight ≤ 100 kg.
Women of child bearing potential have a negative 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.
Recipient of multiple organ transplantation or scheduled for multiple organ transplantation.
Recipient of kidney from a pediatric 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 hematologic 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.
Facility Information:
Facility Name
Maastricht University Medical Center
City
Minderbroedersberg
State/Province
Maastricht
ZIP/Postal Code
6211 LK
Country
Netherlands
Facility Name
Hospital Clínico San Carlos
City
San Carlos
State/Province
Madrid
ZIP/Postal Code
28001
Country
Spain
Facility Name
The Newcastle Upon Tyne Hospital
City
Newcastle
State/Province
metropolitan county of Tyne and Wear
ZIP/Postal Code
NE7 7DN
Country
United Kingdom
12. IPD Sharing Statement
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Study on Delayed Graft Function Using Paired Kidneys
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