NCT01429844

Brief Summary

The purpose of the study is to compare efficacy and safety of two different immunosuppressive regimens for prevention of bronchiolitis obliterans syndrome (BOS) (chronic lung allograft rejection)after lung transplantation: tacrolimus versus cyclosporine, both in combination with mycophenolate mofetil and steroids. The study was powered to detect a 15% reduction in BOS in tacrolimus treated patients. Study design: open-label, randomized, comparative, multi-center, investigator driven

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
274

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Jan 2001

Longer than P75 for phase_3

Geographic Reach
5 countries

13 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2001

Completed
6.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2007

Completed
2.8 years until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2010

Completed
1.1 years until next milestone

First Submitted

Initial submission to the registry

September 5, 2011

Completed
2 days until next milestone

First Posted

Study publicly available on registry

September 7, 2011

Completed
Last Updated

September 7, 2011

Status Verified

September 1, 2011

Enrollment Period

6.8 years

First QC Date

September 5, 2011

Last Update Submit

September 6, 2011

Conditions

Bronchiolitis ObliteransImmunosuppression

Keywords

Calcineurin inhibitorsBronchiolitis obliteransLung transplantationCyclosporineTacrolimusMycophenolateSteroidsChronic rejectionAcute rejectionObliterative bronchiolitis

Outcome Measures

Primary Outcomes (1)

  • Incidence of bronchiolitis obliterans syndrome

    The incidence of patients with bronchiolitis obliterans syndrome (BOS), defined as a sustained fall (for \>1 month) in maximum FEV1 of 20% or more (compared to baseline) over three years post transplant.

    3 years post transplant

Secondary Outcomes (5)

  • Acute allograft rejection

    3 years post transplant

  • Patient and graft survival

    3 years post transplant

  • Incidence and spectrum of infections

    3 years post transplant

  • Renal failure

    3 years post transplant

  • Treatment failure

    3 years post transplant

Study Arms (2)

Tacrolimus

ACTIVE COMPARATOR

Tacrolimus in combination with mycophenolate mofetil and steroids for denovo immunosuppression after lung transplantation

Drug: Tacrolimus

Cyclosporine

ACTIVE COMPARATOR

Cyclopsorine in combination with mycophenolate mofetil and steroids for denovo immunosuppression after lung transplantation

Drug: Cyclosporine

Interventions

TacrolimusDRUG

Tacrolimus therapy was started immediately after transplantation with a continuous intravenous infusion of 0.01-0.03 mg/kg/d. After extubation, the mode of delivery was switched to oral administration (b.i.d.) with doses of 0.05-0.3 mg/kg/d. Tacrolimus doses were adjusted to trough levels. Target C0 (trough) levels were 10-15 ng/ml for the first 3 months after transplantation and 8-12 ng/ml thereafter with dose adjustments according to patient outcome.

Also known as: FK 506, Prograf
Tacrolimus
CyclosporineDRUG

Cyclosporine therapy was started immediately after transplantation with a continuous intravenous infusion of 1-3 mg/kg/d. After extubation the mode of delivery was switched to oral administration (b.i.d. or t.i.d.) with doses of 4-18 mg/kg/d. Cyclosporine doses were adjusted to C0 or C2 levels according to local practice. Target trough levels were 200 - 300 ng/ml for the first 3 months after transplantation and 150 - 200 ng/ml thereafter.

Also known as: CyA, CsA, Cyclosporine A, Sandimmune
Cyclosporine

Eligibility Criteria

Age18 Years - 66 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • male or female recipients of a first heart-lung
  • bilateral or single lung allograft suitable to receive triple immunosuppressive therapy with tacrolimus or cyclosporine, MMF and corticosteroids per standard guidelines
  • Age range = 18-66 years
  • Able to understand the purposes and risks of the study
  • Female patients of child bearing age agreeing to maintain effective birth control practice during the follow-up period

You may not qualify if:

  • need for immunosuppressive regimen other than study medication or received additional organ transplantations
  • Pregnant women, nursing mothers or women unwilling to use adequate contraception
  • Serologic evidence of human immunodeficiency virus, hepatitis B surface antigen or hepatitis C virus antibodies
  • Panresistant infections with Burkholderia cepacia or mycobacteria during the last 12 months preceding lung transplantation
  • Patients with renal insufficiency (creatinine clearance \< 40 ml/min
  • Patients in need of invasive ventilator devices or extracorporeal membrane oxygenation

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (14)

St. Vincent's Hospital

Sydney, NSW 2010, Australia

Location

Allgemeines Krankenhaus Wien

Vienna, 1090, Austria

Location

Hospital Erasme

Brussels, 1070, Belgium

Location

Universitaire Ziekenhuizen

Leuven, 3000, Belgium

Location

Universitätsklinikum Essen

Essen, 45147, Germany

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Universitätsklinikum Jena

Jena, 07740, Germany

Location

Universitätsklinikum Kiel

Kiel, 24105, Germany

Location

Hospital Juan Canalejo

A Coruña, 15006, Spain

Location

Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Reina Sofia

Córdoba, 14004, Spain

Location

Clínica Puerta de Hierro

Madrid, 28035, Spain

Location

Hospital Marques de Valdecilla

Santander, 39008, Spain

Location

Centre hospitalier universitaire vaudois

Lausanne, 1011, Switzerland

Location

Related Publications (13)

  • Aurora P, Edwards LB, Kucheryavaya AY, Christie JD, Dobbels F, Kirk R, Rahmel AO, Stehlik J, Hertz MI. The Registry of the International Society for Heart and Lung Transplantation: thirteenth official pediatric lung and heart-lung transplantation report--2010. J Heart Lung Transplant. 2010 Oct;29(10):1129-41. doi: 10.1016/j.healun.2010.08.008. No abstract available.

    PMID: 20870167BACKGROUND

  • Reichenspurner H, Girgis RE, Robbins RC, Conte JV, Nair RV, Valentine V, Berry GJ, Morris RE, Theodore J, Reitz BA. Obliterative bronchiolitis after lung and heart-lung transplantation. Ann Thorac Surg. 1995 Dec;60(6):1845-53. doi: 10.1016/0003-4975(95)00776-8.

    PMID: 8787504BACKGROUND

  • Snell GI, Boehler A, Glanville AR, McNeil K, Scott JP, Studer SM, Wallwork J, Westall G, Zamora MR, Stewart S. Eleven years on: a clinical update of key areas of the 1996 lung allograft rejection working formulation. J Heart Lung Transplant. 2007 May;26(5):423-30. doi: 10.1016/j.healun.2007.01.040. No abstract available.

    PMID: 17449409BACKGROUND

  • Estenne M, Maurer JR, Boehler A, Egan JJ, Frost A, Hertz M, Mallory GB, Snell GI, Yousem S. Bronchiolitis obliterans syndrome 2001: an update of the diagnostic criteria. J Heart Lung Transplant. 2002 Mar;21(3):297-310. doi: 10.1016/s1053-2498(02)00398-4. No abstract available.

    PMID: 11897517BACKGROUND

  • Hachem RR, Yusen RD, Chakinala MM, Meyers BF, Lynch JP, Aloush AA, Patterson GA, Trulock EP. A randomized controlled trial of tacrolimus versus cyclosporine after lung transplantation. J Heart Lung Transplant. 2007 Oct;26(10):1012-8. doi: 10.1016/j.healun.2007.07.027.

    PMID: 17919621BACKGROUND

  • Keenan RJ, Konishi H, Kawai A, Paradis IL, Nunley DR, Iacono AT, Hardesty RL, Weyant RJ, Griffith BP. Clinical trial of tacrolimus versus cyclosporine in lung transplantation. Ann Thorac Surg. 1995 Sep;60(3):580-4; discussion 584-5. doi: 10.1016/0003-4975(95)00407-C.

    PMID: 7545889BACKGROUND

  • Treede H, Klepetko W, Reichenspurner H, Zuckermann A, Meiser B, Birsan T, Wisser W, Reichert B; Munich and Vienna Lung Transplant Group. Tacrolimus versus cyclosporine after lung transplantation: a prospective, open, randomized two-center trial comparing two different immunosuppressive protocols. J Heart Lung Transplant. 2001 May;20(5):511-7. doi: 10.1016/s1053-2498(01)00244-3.

    PMID: 11343977BACKGROUND

  • Zuckermann A, Reichenspurner H, Birsan T, Treede H, Deviatko E, Reichart B, Klepetko W. Cyclosporine A versus tacrolimus in combination with mycophenolate mofetil and steroids as primary immunosuppression after lung transplantation: one-year results of a 2-center prospective randomized trial. J Thorac Cardiovasc Surg. 2003 Apr;125(4):891-900. doi: 10.1067/mtc.2003.71.

    PMID: 12698153BACKGROUND

  • Sarahrudi K, Estenne M, Corris P, Niedermayer J, Knoop C, Glanville A, Chaparro C, Verleden G, Gerbase MW, Venuta F, Bottcher H, Aubert JD, Levvey B, Reichenspurner H, Auterith A, Klepetko W. International experience with conversion from cyclosporine to tacrolimus for acute and chronic lung allograft rejection. J Thorac Cardiovasc Surg. 2004 Apr;127(4):1126-32. doi: 10.1016/j.jtcvs.2003.11.009.

    PMID: 15052212BACKGROUND

  • Vitulo P, Oggionni T, Cascina A, Arbustini E, D'Armini AM, Rinaldi M, Meloni F, Rossi A, Vigano M. Efficacy of tacrolimus rescue therapy in refractory acute rejection after lung transplantation. J Heart Lung Transplant. 2002 Apr;21(4):435-9. doi: 10.1016/s1053-2498(01)00379-5.

    PMID: 11927219BACKGROUND

  • McNeil K, Glanville AR, Wahlers T, Knoop C, Speich R, Mamelok RD, Maurer J, Ives J, Corris PA. Comparison of mycophenolate mofetil and azathioprine for prevention of bronchiolitis obliterans syndrome in de novo lung transplant recipients. Transplantation. 2006 Apr 15;81(7):998-1003. doi: 10.1097/01.tp.0000202755.33883.61.

    PMID: 16612275BACKGROUND

  • Orens JB, Estenne M, Arcasoy S, Conte JV, Corris P, Egan JJ, Egan T, Keshavjee S, Knoop C, Kotloff R, Martinez FJ, Nathan S, Palmer S, Patterson A, Singer L, Snell G, Studer S, Vachiery JL, Glanville AR; Pulmonary Scientific Council of the International Society for Heart and Lung Transplantation. International guidelines for the selection of lung transplant candidates: 2006 update--a consensus report from the Pulmonary Scientific Council of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2006 Jul;25(7):745-55. doi: 10.1016/j.healun.2006.03.011. No abstract available.

    PMID: 16818116BACKGROUND

  • Shyu S, Dew MA, Pilewski JM, DeVito Dabbs AJ, Zaldonis DB, Studer SM, Crespo MM, Toyoda Y, Bermudez CA, McCurry KR. Five-year outcomes with alemtuzumab induction after lung transplantation. J Heart Lung Transplant. 2011 Jul;30(7):743-54. doi: 10.1016/j.healun.2011.01.714. Epub 2011 Mar 21.

    PMID: 21420318BACKGROUND

Related Links

MeSH Terms

Conditions

Bronchiolitis Obliterans

Interventions

TacrolimusCyclosporine

Condition Hierarchy (Ancestors)

BronchiolitisBronchitisBronchial DiseasesRespiratory Tract DiseasesLung Diseases, ObstructiveLung Diseases

Intervention Hierarchy (Ancestors)

MacrolidesLactonesOrganic ChemicalsCyclosporinsPeptides, CyclicMacrocyclic CompoundsPolycyclic CompoundsPeptidesAmino Acids, Peptides, and Proteins

Study Officials

  • Hermann Reichenspurner, MD, PhD

    Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany

    PRINCIPAL INVESTIGATOR

  • Allan Glanville, MD, PhD

    St Vincent's Hospital - Sydney, Australia

    STUDY CHAIR

  • Hendrik Treede, MD

    Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Prof. Dr. med. Hermann Reichenspurner, PhD

Study Record Dates

First Submitted

September 5, 2011

First Posted

September 7, 2011

Study Start

January 1, 2001

Primary Completion

October 1, 2007

Study Completion

August 1, 2010

Last Updated

September 7, 2011

Record last verified: 2011-09

Locations

CH(1)AU(1)BE(2)DE(4)ES(5)