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Viral Load Guided Immunosuppression After Lung Transplantation (VIGILung)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04198506
Recruitment Status : Not yet recruiting
First Posted : December 13, 2019
Last Update Posted : March 17, 2020
Sponsor:
Information provided by (Responsible Party):
Philipps University Marburg Medical Center

Brief Summary:
The VIGILung study is an open-label, randomized, multicenter trial in lung transplant recipients to investigate the safety and efficacy of personalized immunosuppression guided by DNA monitoring of Torque-Teno-Virus (TTV). The aim of the study is to investigate an individual adaptation of the calcineurin inhibitor tacrolimus (tailored calcineurin inhibitor dosing) by a non-invasive biomarker (TTV viral load in whole blood) compared to conventional calcineurin inhibitor dosing. Indicator for toxicity will be the glomerular filtration rate (GFR), which will be estimated using the CKD-EPI formula. 250 patients (age ≥ 18 years) with 21 to 42 days after de novo lung transplantation (bilateral or combined) will be screened as possible subjects eligible for the study. N = 144 patients have to be randomized in two study arms. In Arm 1 tacrolimus doses will be adapted according to the tacrolimus blood level (conventional therapeutic drug monitoring - TDM) and additionally depending on TTV viral load. In Arm 2 tacrolimus doses will be adapted according to TDM.

Condition or disease Intervention/treatment Phase
Transplantation Lung Other: Tailored tacrolimus dosing Other: Conventional tacrolimus dosing Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 144 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Viral Load Guided Immunosuppression After Lung Transplantation, an Open-label, Randomized, Controlled, Parallel-group, Multicenter Trial
Estimated Study Start Date : May 1, 2020
Estimated Primary Completion Date : December 1, 2025
Estimated Study Completion Date : December 1, 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Tacrolimus

Arm Intervention/treatment
Experimental: Tailored tacrolimus dosing
Tacrolimus doses will be adapted according to tacrolimus blood level (conventional therapeutic drug monitoring - TDM) and additionally depending on TTV viral load.
Other: Tailored tacrolimus dosing
Tacrolimus doses will be adapted according to tacrolimus blood level (conventional therapeutic drug monitoring -TDM) and additionally depending on TTV viral load.

Active Comparator: Conventional tacrolimus dosing
Tacrolimus doses will be adapted according to tacrolimus blood level (conventional therapeutic drug monitoring - TDM).
Other: Conventional tacrolimus dosing
Tacrolimus doses will be adapted according to tacrolimus blood level (conventional therapeutic drug monitoring - TDM).




Primary Outcome Measures :
  1. ΔGFR change of the glomerular filtration rate GFR [ Time Frame: Between randomization and 12 months thereafter ]
    The primary efficacy endpoint ΔGFR is defined as the change of the glomerular filtration rate GFR between randomization and 12 months thereafter. GFR will be estimated using the CKD-EPI formula.


Secondary Outcome Measures :
  1. GFR (CKD-EPI) [ Time Frame: 1 and 2 months after transplantation (screening visits) and 0, 3, 6, 9 and 12 months after randomization ]
    Glomerular filtration rate (the Chronic Kidney Disease Epidemiology Collaboration - CKD-EPI) formula

  2. GFR (Cystatin) [ Time Frame: Screening visits and 0, 3, 6, 9 and 12 months after randomization ]
    Glomerular filtration rate (Cystatin)

  3. Number of biopsy-proven acute cellular rejection (grade A1 or higher) [ Time Frame: 12 months after randomization ]
  4. Number of episodes of biopsy-proven lymphocytic bronchitis (grade B1R or higher) [ Time Frame: 12 months after randomization ]
  5. Number of cytomegalovirus (CMV)-infections and CMV-disease episodes [ Time Frame: 12 months after randomization ]
  6. Number of community-acquired respiratory viral infections (CARV) [ Time Frame: 12 months after randomization ]
  7. Number of fungal and bacterial infections [ Time Frame: 12 months after randomization ]
  8. Number of unscheduled or emergency hospitalizations [ Time Frame: 12 months after randomization ]
  9. Number of ICU admissions [ Time Frame: 12 months after randomization ]
  10. Quality of life questionnaire [ Time Frame: Screening visits and 0, 3, 6, 9 and 12 months after randomization ]
    European Quality of Life 5 Dimensions - EQ-5D

  11. New or progressive malignancy [ Time Frame: 12 months after randomization ]
  12. Median tacrolimus trough levels [ Time Frame: Screening visits and 0, 3, 6, 9 and 12 months after randomization ]
  13. Tacrolimus dose [ Time Frame: Screening visits and 0, 3, 6, 9 and 12 months after randomization ]
  14. Number of changes (increase or decrease) in target trough levels of tacrolimus [ Time Frame: Screening visits and 0, 3, 6, 9 and 12 months after randomization ]
  15. Exercise capacity (6-Min Walk Test - 6MWT) [ Time Frame: At randomization and 12 months thereafter ]
  16. CD4-Lymphocytes counts [ Time Frame: 0, 6 and 12 months after randomization ]
  17. Donor specific antibodies [ Time Frame: 0, 6 and 12 months after randomization ]
  18. FEV1 in % best value [ Time Frame: Screening visits and 0, 3, 6, 9 and 12 months after randomization ]
  19. Incidence of chronic lung allograft dysfunction [ Time Frame: Between randomization and 12 months thereafter ]
  20. IgG-level [ Time Frame: 0, 6 and 12 months after randomization ]
  21. Use of rescue immunotherapy (defined by the use of ATG, Rituximab, Alemtuzumab, plasma exchange, immunoadsorption) [ Time Frame: 12 months after randomization ]
  22. Death or re-do transplantation [ Time Frame: 12 months after randomization ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients 21 to 42 days after de novo lung transplantation (bilateral or combined)
  2. Age ≥ 18 years
  3. Tacrolimus based immunosuppression
  4. Written informed consent
  5. Detectable TTV load at randomization (>2,7 log 10)
  6. Negative serum pregnancy test in women of childbearing potential
  7. Women of childbearing capacity must agree to maintain highly effective methods of contraception by practicing abstinence or by using at least two methods of birth control from the date of consent through the end of the study. If abstinence is not practiced, a combination of hormonal contraceptive (oral, injectable or implants) and a barrier method (condom, diaphragm with a vaginal spermicidal agent) has to be used

Exclusion Criteria:

  1. History or high-risk of obstructive airway complications after lung transplantation
  2. Respiratory failure (need for oxygen therapy or ventilation at screening after lung transplantation)
  3. Inability to undergo transbronchial biopsy
  4. Advanced kidney failure (GFR CKD-EPI <30 ml/min/1.73m²) at inclusion and/or current renal replacement therapy at inclusion or randomization
  5. Advanced liver cirrhosis (CHILD-Pugh Score C) after lung transplantation
  6. Fluctuating tacrolimus drug levels (less than 20% in target range after transplantation)
  7. Symptoms of significant mental illness and with inability to cooperate or communicate with the investigator
  8. Unlikeliness to comply with the study requirements
  9. HIV positivity
  10. Evidence of unsolved drug or alcohol addiction
  11. Breastfeeding women
  12. Simultaneous participation in other clinical trials if not permitted by the steering committee

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04198506


Contacts
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Contact: Jens Gottlieb, Prof. MD +49 (0) 511-532-4601 gottlieb.jens@mh-hannover.de

Locations
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Germany
Klinik für Pneumologie OE 6870, Medizinische Hochschule Hannover
Hannover, Germany, 30625
Contact: Jens Gottlieb, Prof. MD    +49 (0) 511-532-4601    gottlieb.jens@mh-hannover.de   
Sponsors and Collaborators
Philipps University Marburg Medical Center
Investigators
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Principal Investigator: Jens Gottlieb, Prof. MD Klinik für Pneumologie OE 6870, Medizinische Hochschule Hannover (MHH)

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Responsible Party: Philipps University Marburg Medical Center
ClinicalTrials.gov Identifier: NCT04198506    
Other Study ID Numbers: KKS-256
2019-001770-29 ( EudraCT Number )
First Posted: December 13, 2019    Key Record Dates
Last Update Posted: March 17, 2020
Last Verified: December 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Philipps University Marburg Medical Center:
lung transplantation
dosing immunosuppression
toxicity
Additional relevant MeSH terms:
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Tacrolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action