Reparixin in Prevention of Delayed Graft Function After Kidney Transplantation

NCT00248040 | Completed Phase 2 Results

• 1 other identifier: REP0204
• Study Type: interventional
• Target: 80
• Locations: 4 countries
• Sites: 9

Brief Summary

The chemokine CXCL8 plays a key role in the recruitment and activation of polymorphonuclear neutrophils in post-ischemia reperfusion injury after solid organ transplantation. Reparixin is a novel, specific inhibitor of CXCL8. This study is configured to explore the safety and efficacy of reparixin in preventing the delayed graft function (DGF) after kidney transplantation.

Conditions

Ischemia-Reperfusion Injury; Kidney Diseases

Keywords

Kidney transplantation; Reperfusion Injury; Survival

Outcome Measures

Primary Outcomes (1)

• Creatinine Clearance (CrCl) in the Immediate Post-transplant Period

  CrCl was determined by two 60 minute urine collections, during the time intervals 1-3 and 10-12 hours of allograft reperfusion. Blood was withdrawn at the midpoint of each urine collection. CrCl at each timepoint was calculated according to the formula: creatinine clearance (mL/minutes) = urine creatinine (mmol/L) x urine volume (mL) / serum creatinine (mmol/L) x time of collection (minutes) An average was to be calculated from the two 60 minute values in each interval.

  1-3 and 10-12 hours post allograft reperfusion

Secondary Outcomes (13)

• Renal Function Tests - Serum Creatinine

  daily up to day 7 post-transplant or hospital discharge

• Renal Function Tests - Calculated Glomerular Filtration Rate

  from Day 1 up to 7 days post-transplant or up to hospital discharge

• Renal Function Tests - Urine Output

  from Day 1 up to 7 days post-transplant or up to hospital discharge

• Number of Patients Requiring Dialysis Within 7 Days Post-transplant

  up to day 7 post-transplant

• Number of Days on Dialysis Before Resuming Kidney Function

  up to Day 7 post-transplant

Study Arms (3)

reparixin group - continuous infusion

EXPERIMENTAL

Continuous iv infusion into a (high flow) central vein (or through an arterio-venous fistula) by an infusion pump. A dose of 2.772 mg/kg/h was administered for12 hours.

Drug: Reparixin continuous infusion

reparixin group - intermittent infusion

EXPERIMENTAL

Intermittent iv infusion into a (high flow) central vein (or through an arterio-venous fistula) by an infusion pump. A dose of 2.244 mg/kg was administered over a 30-minute period, followed by a 1.5-hour interval. Twelve doses were administered over a total period of 22.5 hours.

Drug: reparixin intermittent infusion

placebo infusion

PLACEBO COMPARATOR

Continuous/intermittent iv infusion of a volume/schedule matched saline into a (high flow) central vein (or through an arterio-venous fistula) by an infusion pump.

Other: placebo infusion

Interventions

Reparixin continuous infusion DRUG

The Investigational Product was administered as an intravenous infusion into a (high flow) central vein or through an arterio-venous fistula, by an infusion pump adequate to provide reliable infusion rates, as per treatment schedule. Total infusion volume did not exceed 500 mL/24 hours. A dose of 2.772 mg/kg body weight/hour was to be administered for 12 hours. Placebo was volume/schedule matched saline.

Also known as: REP

reparixin group - continuous infusion

reparixin intermittent infusion DRUG

A dose of 2.244 mg/kg body weight was to be administered over a 30-minute period, followed by a 1.5-hour interval. Twelve doses were to be administered over a total period of 22.5 hours. Placebo was volume/schedule matched saline.

Also known as: REP

reparixin group - intermittent infusion

placebo infusion OTHER

placebo was volume/schedule matched saline

placebo infusion

Eligibility Criteria

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

You may qualify if:

• Male and female patients accepted and listed for renal transplantation due to end stage renal disease (ESRD)
• Planned isolated single kidney transplant from a non-living donor with brain death
• Recipients of a kidney maintained in cold storage
• Recipients at risk of developing DGF
• Planned induction with steroids + mycophenolate mofetil (MMF) or mycophenolic acid + biological induction
• Patient willing and able to comply with the protocol procedures for the duration of the study, including scheduled follow-up visits and examinations
• Patient given written informed consent, prior to any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care

You may not qualify if:

• Recipients of an intended multiple organ transplant
• Recipients of a kidney from a living donor
• Recipients of a kidney from a non-heart beating donor
• Recipients of double kidney transplant
• Re-transplant \>2
• Recipients of a kidney maintained by pulsatile machine perfusion
• Concurrent sepsis
• Recipients with hepatic dysfunction at the time of transplant
• Clinical contraindications to central line access, or arteriovenous fistula, if any, not suitable for infusion of investigational product
• Hypersensitivity to non steroidal anti-inflammatory drugs (NSAIDs)
• Patients simultaneously participating in any other clinical trials involving an investigational drug not yet authorized for use in kidney transplant
• Pregnant or breast-feeding women

Sponsors & Collaborators

• Dompé Farmaceutici S.p.A: lead

Study Sites (9)

Transplant Center, University of Minnesota Medical School

Minneapolis, Minnesota, 55455, United States

Location

Division of Transplantation, Drexel University College of Medicine

Philadelphia, Pennsylvania, 19102, United States

Location

Service de Nephrologie et Transplantation, Hopital Lapeyronie, Centre Hospitalier Universitaire Montpellier

Montpellier, 34295 Cedex 5, France

Location

Service de Transplantation et Soins Intensifs Nephrologiques, Hopital Necker

Paris, 75743 Cedex 15, France

Location

Divisione di Nefrologia e Dialisi, Ospedali Riuniti di Bergamo

Bergamo, 24128, Italy

Location

Divisione di Nefrologia e Dialisi, Azienda Ospedaliera Spedali Civili di Brescia

Brescia, 25123, Italy

Location

Università degli Studi di Padova, Clinica Chirurgica III

Padua, 35128, Italy

Location

Renal Transplant Unit, Hopital Clinic i Provincial de Barcelona

Barcelona, 08036, Spain

Location

Division of Nephrology, Institut Catala de la Salut, Ciutat Sanitaria i Universitaria de Bellvitge

Barcelona, 08907, Spain

Location

MeSH Terms

Conditions

Reperfusion Injury; Kidney Diseases

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Clinical Development & Operations
• Organization: Dompé farmaceutici s.p.a.

clinical.trials@dompe.com

+39 02 583831

Study Officials

• Giuseppe Remuzzi, MD

  A.O. Ospedale Papa Giovanni XXIII

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2005
• First Posted: November 3, 2005
• Study Start: October 1, 2005
• Primary Completion: May 1, 2008
• Study Completion: June 1, 2008
• Last Updated: January 10, 2024
• Results First Posted: April 14, 2020

Record last verified: 2020-09

Locations

FR (2); US (2); ES (2); IT (3)