C1INH Inhibitor Preoperative and Post Kidney Transplant to Prevent DGF & IRI

NCT02134314 | Completed Phase 1 Results DMC

• 2 other identifiers: C1INH (Berinert) for DGFIND15806
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

The use of C1INH (Berinert) in patients receiving deceased donor kidney transplants with high risk for delayed graft function (DGF) may show significant improvement in outcomes post transplant compared with patients that do not receive C1INH treatment. Complement activation has been detected in animal models and human kidneys with ischemic reperfusion injury (IRI) and inflammatory cell infiltrates. By blocking complement activation the investigators hope to improve kidney graft function post transplant in these recipients.

Conditions

End Stage Renal Disease; Kidney Failure; Delayed Graft Function; Ischemic Reperfusion Injury

Keywords

ESRD (End Stage Renal Disease); CKD (Chronic Kidney Disease); Kidney Transplant; ECD; delayed graft function; chronic kidney disease; expanded-criteria donor; end stage renal disease

Outcome Measures

Primary Outcomes (4)

• Number of Patients Enrolled With Serum Creatinine >3mg/dL on Postoperative Day 5.

  Number of participants in the C1INH and placebo groups with serum creatinine \>3mg/dL on postoperative day 5

  First 7 days post-transplant

• Number of Patients Enrolled Who Require at Least One Session of Dialysis in the First 7 Days Post Transplant.

  The proportion of patients enrolled who require at least one session of dialysis in the first 7 days post transplant (excluding those who are dialyzed for hyperkalemia).

  First 7 days post-transplant

• Number of Patients With Serum Creatinine Reduction Ratio of < 30% From 24 to 48 Hours Post-transplant.

  Number of patients in the C1INH and placebo groups with serum creatinine reduction of \< 30% from 24 to 48 hours post-transplant.

  First 7 days post-transplant

• Number of Dialysis Sessions Per Patient in the First 7 Days Post Transplant.

  Mean quantity of dialysis sessions per patient in the first 7 days post transplant.

  First 7 days post-transplant

Secondary Outcomes (5)

• Serum Creatinine

  Up to 90 days post-transplant

• Creatinine Clearance

  Up to 90 days post-transplant

• 24h Urine Output

  24 hours post-transplant

• Mean Number of Patients on Dialysis

  15 to 30 days post-transplantation

• Number of Patients With Delayed Graft Function (DGF) (Categorized by DGF Scale)

  First 7 days post-transplant

Other Outcomes (4)

• Overall Incidence of Serious Adverse Events

  Up to 9 months post-transplant

• Patient Survival

  Up to 90 days post-transplant

• Rate of Acute Cellular Rejection (ACR)

  Up to 90 days post-transplant

Study Arms (2)

C1-Inhibitor (Berinert) (Human) (C1INH)

EXPERIMENTAL

35 patients will receive C1 esterase inhibitor in addition to standard of care immunosuppressive therapy.

Drug: C1 Esterase Inhibitor

Normal Saline

PLACEBO COMPARATOR

35 patients will receive placebo in addition to standard of care immunosuppressive therapy.

Drug: Placebo

Interventions

C1 Esterase Inhibitor DRUG

C1 Esterase Inhibitor 50 units per kilogram intravenous infusion administered on day of transplant, and another dose at 24 hours post-operatively. Total: 2 doses

Also known as: Berinert (C1INH)

C1-Inhibitor (Berinert) (Human) (C1INH)

Placebo DRUG

Placebo medication identical to study drug (C1 esterase inhibitor) volume will be administered on day of transplant, and another dose at 24 hours post-operatively. Total: 2 doses

Also known as: Normal Saline (0.9%NaCl)

Normal Saline

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• yrs of age; recipient of ECD/DCD/ECD\&DCD with risk index 3-8 for DGF based on specific criteria
• recipient who are ABO compatible with donor allograft
• pretransplant with meningococcal vaccination
• understand and sign a written consent prior to any study specific procedure.
• Risk index (minimum 3- maximum 8):
• DGF scale: Donor Age (\<40yr = 0, 41-49yr = 1, 50-54yr = 2, 55-59yr = 3, \>60yr=6), Cold Ischemia Time (0-12= 0, 13-18=1, 19-24=2, 24-30=3, 31-36=4, \>37=6; Recipient Race (nonblack = 0, black =1); Donor death due to Cerebrovascular Accident (CVA) (donor age \<50yrs = 0, donor age \>50yrs = 3).

You may not qualify if:

• patients with known prothrombotic disorder (e.g. factor V leiden)
• history of thrombosis or hypercoagulable state excluding access clotting
• history of administration of C1INH containing products or recombinant C1INH within 15 days prior to study entry
• patients with known contraindication to treatment with C1INH
• patients with abnormal coagulation function (INR \>2, partial thromboplastin time (PTT) \> 50, platelets \<80,000)
• who are not on anti-coagulation
• patients with known active presence of malignancies
• Polymerase chain reaction (PCR) positive for hep B/hep C/or HIV
• preemptive kidney transplantation recipient
• recipients of multi-organ transplants (kidney and any other organ)
• recipients of kidney allograft from DD who: cold ischemia time (CIT) \<18h, terminal serum creatinine \</= 1mg/dl, recipient of kidney allograft that was on pump preservation for any period prior to transplantation, recipient of kidney allograft from a living donor, female subject who are pregnant or lactating.

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead

Study Sites (1)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Related Publications (4)

• Dalle Lucca JJ, Li Y, Simovic M, Pusateri AE, Falabella M, Dubick MA, Tsokos GC. Effects of C1 inhibitor on tissue damage in a porcine model of controlled hemorrhage. Shock. 2012 Jul;38(1):82-91. doi: 10.1097/SHK.0b013e31825a3522.

  PMID: 22683724 BACKGROUND

• Pascual J, Zamora J, Pirsch JD. A systematic review of kidney transplantation from expanded criteria donors. Am J Kidney Dis. 2008 Sep;52(3):553-86. doi: 10.1053/j.ajkd.2008.06.005.

  PMID: 18725015 BACKGROUND

• Castellano G, Melchiorre R, Loverre A, Ditonno P, Montinaro V, Rossini M, Divella C, Battaglia M, Lucarelli G, Annunziata G, Palazzo S, Selvaggi FP, Staffieri F, Crovace A, Daha MR, Mannesse M, van Wetering S, Paolo Schena F, Grandaliano G. Therapeutic targeting of classical and lectin pathways of complement protects from ischemia-reperfusion-induced renal damage. Am J Pathol. 2010 Apr;176(4):1648-59. doi: 10.2353/ajpath.2010.090276. Epub 2010 Feb 11.

  PMID: 20150432 BACKGROUND

• Giral-Classe M, Hourmant M, Cantarovich D, Dantal J, Blancho G, Daguin P, Ancelet D, Soulillou JP. Delayed graft function of more than six days strongly decreases long-term survival of transplanted kidneys. Kidney Int. 1998 Sep;54(3):972-8. doi: 10.1046/j.1523-1755.1998.00071.x.

  PMID: 9734625 BACKGROUND

Related Links

• Cedars Sinai Medical Center Kidney Transplantation
• Information of C1INH (Berinert)

MeSH Terms

Conditions

Kidney Failure, Chronic; Renal Insufficiency; Delayed Graft Function; Renal Insufficiency, Chronic

Interventions

Complement C1 Inhibitor Protein; Saline Solution; Sodium Chloride

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Complement C1 Inactivator Proteins; Serpins; Peptides; Amino Acids, Peptides, and Proteins; Complement Inactivator Proteins; Complement System Proteins; Immunoproteins; Blood Proteins; Proteins; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Limitations and Caveats

The limitations of this study include the small sample size and single-center performance. However, the patient population was balanced between the two groups and donor organ characteristics, including implantation biopsies, were similar.

Results Point of Contact

• Title: Noriko Ammerman, PharmD
• Organization: Cedars-Sinai Medical Center

noriko.ammerman@cshs.org

310-248-8186

Study Officials

• Stanley C Jordan, MD

  Cedars-Sinai Medical Center, Los Angeles, CA

  PRINCIPAL INVESTIGATOR

• Ashley Vo, PharmD

  Cedars-Sinai Medical Center, Los Angeles, CA

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Director, Kidney Transplant Program; Director of Transplant Immunology and Nephrology

Study Record Dates

• First Submitted: February 19, 2014
• First Posted: May 9, 2014
• Study Start: September 1, 2014
• Primary Completion: March 13, 2017
• Study Completion: March 13, 2017
• Last Updated: June 25, 2018
• Results First Posted: June 25, 2018

Record last verified: 2018-06

Locations

US (1)