Study on Delayed Graft Function Using Paired Kidneys

Delayed Graft Function Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01561599
• Other study ID #: 004-09
• Secondary ID: 2010-019243-192R
• Status: Active, not recruiting
• Phase: Phase 2
• First received: March 21, 2012
• Last updated: February 18, 2016
• Start date: August 2011
• Est. completion date: May 2016

Study information

• Verified date: February 2016
• Source: Angion Biomedica Corp
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Medicines Evaluation Board (MEB)Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 12
• Est. completion date: May 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Delayed Graft Function

Intervention

Drug:
• BB3
Daily intravenous administration of 2mg/kg for 4 days
• Normal Saline
Daily intravenous administration for four (4) days. The volume of normal saline will vary by estimated weight.

Locations

Country	Name	City	State
Netherlands	Maastricht University Medical Center	Minderbroedersberg	Maastricht
Spain	Hospital Clínico San Carlos	San Carlos	Madrid
United Kingdom	The Newcastle Upon Tyne Hospital	Newcastle	metropolitan county of Tyne and Wear

Sponsors (2)

Lead Sponsor	Collaborator
Angion Biomedica Corp	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Countries where clinical trial is conducted

Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	7 days	No
Secondary	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.	28 days	No
Secondary	Creatinine clearance	Calculated creatinine clearance at days 14 and 28	28 days	No
Secondary	Incidence of delayed graft function	Incidence of delayed graft function (required dialysis due to inadequate renal function during the first 7 days after transplantation).	7 days	No
Secondary	Number of dialysis sessions	Number of dialysis sessions through day 7, 14, and 28	28 days	No
Secondary	Mean total daily urine output	Mean total daily urine output through day 14	14 days	No
Secondary	Daily serum creatinine	Daily serum creatinine at days 1 to 7	7 days	No
Secondary	Mean serum creatinine	Mean serum creatinine at days 4, 7, 10, 14, and 28	28 days	No
Secondary	Length of hospitalization following transplantation	Length of hospitalization following transplantation	28 days	No
Secondary	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	12 months	No