Viral Load Guided Immunosuppression After Lung Transplantation

NCT04198506 | Completed DMC

• 2 other identifiers: KKS-2562019-001770-29
• Study Type: interventional
• Target: 146
• Locations: 2 countries
• Sites: 2

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.

Conditions

Transplantation Lung

Keywords

lung transplantation; dosing immunosuppression; toxicity

Outcome Measures

Primary Outcomes (1)

• ΔGFR change of the glomerular filtration rate GFR

  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.

  Between randomization and 12 months thereafter

Secondary Outcomes (23)

• GFR (CKD-EPI)

  1 and 2 months after transplantation (screening visits) and 0, 3, 6, 9 and 12 months after randomization

• GFR (Cystatin)

  At randomization and 12 months after randomization

• proportion of patients with biopsy-proven acute cellular rejection (grade A1 or higher)

  Between randomization and 12 months after randomization

• proportion of patients with an episode of biopsy-proven lymphocytic bronchitis (grade B1R or higher)

  Between randomization and 12 months after randomization

• proportion of patients with cytomegalovirus (CMV)-infection and number of CMV-disease episodes

  Between randomization and 12 months after randomization

Study Arms (2)

Tailored tacrolimus dosing

EXPERIMENTAL

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

Conventional tacrolimus dosing

ACTIVE COMPARATOR

Tacrolimus doses will be adapted according to tacrolimus blood level (conventional therapeutic drug monitoring - TDM).

Other: Conventional tacrolimus dosing

Interventions

Tailored tacrolimus dosing OTHER

Tacrolimus doses will be adapted according to tacrolimus blood level (conventional therapeutic drug monitoring -TDM) and additionally depending on TTV viral load.

Tailored tacrolimus dosing

Conventional tacrolimus dosing OTHER

Tacrolimus doses will be adapted according to tacrolimus blood level (conventional therapeutic drug monitoring - TDM).

Conventional tacrolimus dosing

Eligibility Criteria

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

You may qualify if:

• patients 21 to 42 days after primary de novo lung transplantation (bilateral including combined)
• age ≥ 18 years
• tacrolimus based immunosuppression
• written informed consent
• detectable TTV load at randomization (\>2,7 log 10)
• negative serum pregnancy test in women of childbearing potential.
• 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.

You may not qualify if:

• patients after unilateral or re-do lung transplantation
• history or high-risk of obstructive airway complications after lung transplantation
• respiratory failure (need for oxygen therapy or ventilation at screening after lung transplantation)
• inability to undergo transbronchial biopsy
• advanced liver cirrhosis (CHILD-Pugh Score C) after lung transplantation
• fluctuating tacrolimus drug levels (less than 20% in target range after transplantation)
• symptoms of significant mental illness and with inability to cooperate or communicate with the investigator.
• unlikeliness to comply with the study requirements
• HIV positivity
• evidence of unsolved drug or alcohol addiction
• breastfeeding women
• simultaneous participation in other clinical trials if not permitted by the steering committee

Sponsors & Collaborators

• Philipps University Marburg: lead

Study Sites (2)

Medizinische Universität Wien, Klinische Abteilung für Thoraxchirurgie

Vienna, 1090, Austria

Location

Klinik für Pneumologie OE 6870, Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Related Publications (1)

• Gottlieb J, Reuss A, Mayer K, Weide K, Schade-Brittinger C, Hoyer S, Jaksch P. Viral load-guided immunosuppression after lung transplantation (VIGILung)-study protocol for a randomized controlled trial. Trials. 2021 Jan 11;22(1):48. doi: 10.1186/s13063-020-04985-w.

  PMID: 33430927 RESULT

Study Officials

• Jens Gottlieb, Prof. MD

  Klinik für Pneumologie OE 6870, Medizinische Hochschule Hannover (MHH)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2019
• First Posted: December 13, 2019
• Study Start: August 5, 2020
• Primary Completion: March 7, 2025
• Study Completion: March 10, 2025
• Last Updated: March 30, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Time Frame: data will be available Begin: one year after publication of results. End: maximum ten years after publication of results
• Access Criteria: Approval and release by the steering committee

Locations

AU (1); DE (1)