rATG Versus rATG Combined With Intravenous Immunoglobulin (IVIG) Induction Immunosuppression in HLA Incompatible Transplantation (INHIBIT) (INHIBIT)

August 13, 2024 updated by: Prof. Ondřej Viklický, M.D., Ph.D., Institute for Clinical and Experimental Medicine

rATG Versus rATG Combined With IVIG Induction Immunosuppression in HLA Incompatible Transplantation

This study aims to prove similar efficacy of PE/rATG (intervention) and PE/rATG/IVIG (centre standard of care) induction regimens to prevent biopsy proven antibody-mediated changes and TCMR as composite endpoint within 12 months after HLA incompatible kidney transplantation.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

There have been no published clinical studies evaluating rATG/IVIG induction protocol in comparison with rATG alone in defined cohort of HLA incompatible kidney transplant recipients. Prescribing IVIG in management of prevention of transplant rejection is considered off-label use, however IVIG remains part of induction protocols in many transplant centres. IVIG therapy is demanding due to high cost and limited resources of these human origin products. Trial participants will be end-stage renal disease (ESRD) patients listed for deceased donor / living donor kidney transplantation with anti HLA antibody screening performed within 12 months before transplantation and with last DSA 1 000 - 5 000 Mean Fluorescence Intensity (MFI) and negative CDC (Complement-dependent cytotoxicity crossmatch test) prior to transplantation. Participants will be randomized into one of the treatment groups (PE/PP(Plasmapheresis) + rATG + IVIG, PE/PP + rATG) and as a primary outcome a composite endpoint defined as occurrence of antibody- or T-cell mediated rejection within 12 months after transplantation will be evaluated.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
17

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Czechia
      • Prague, Czechia, 140 21
        • Institute for Clinical and Experimental Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Primary deceased donor or living donor kidney transplantation (first transplantation or re-transplantation)
  • Recipient age ≥ 18 years and < 70 years
  • Donor age < 70 years
  • Written Informed Consent and Consent for Processing Personal Data
  • Last anti-HLA screening no longer than 12 months with positive results
  • MFI DSA 1 000 - 5 000 (anti-HLA A, B, DR), MFI DSA 1000-15000 for anti DQ when available at randomization)

Exclusion Criteria:

  • Combined kidney transplantation with another organ
  • Immunosuppressive therapy up to 6 months before transplantation
  • AB0i (AB0 incompatible) transplantation
  • Women in childbearing potential without adequate contraception
  • HIV positivity
  • Leukopenia < 3 000, thrombocytopenia < 75 000
  • Tuberculosis history
  • Anti-HCV (Hepatitis C Virus) positivity, HBsAg (Hepatitis B Surface Antigen) positivity or HBV (Hepatitis B Virus) DNA positivity
  • DSA (anti A, B, DR) measured by Luminex with MFI > 5 000 known at screening prior to transplant, anti DQ > 15000 if known
  • FACS (flow-cytometry) T and B crossmatch positivity known at screening prior to transplant
  • Positive CDC prior to transplantation
  • Planned PP/PE and RTX (Rituximab) treatment post-transplant
  • Advanced liver disease (Child-Pugh C or laboratory values of ALT or AST more than 3 times upper limit of normal range)
  • Pregnancy, breastfeeding
  • Study medication is contraindicated according to the SmPC
  • Patient is enrolled in other clinical trial

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: PE/rATG
Study participants will undergo therapeutic plasma exchange (PE, 1 plasma volume) before the transplant surgery and receive rATG (Thymoglobuline®) induction (1.5 mg/kg intraoperatively and 1 mg/kg when possible daily within first week up to cumulative dose 5-7 mg/kg).
Drug: Thymoglobulin
All patients will receive 1.5 mg/kg intraoperatively and 1 mg/kg when possible daily within first week up to cumulative dose 5-7 mg/kg.
Other Names:
  • rATG
Other: Plasma Exchange
All patient will undergo Plasma Exchange before transplantation.
Other Names:
  • PE
Active Comparator: PE/rATG/IVIG
Study participants will undergo therapeutic plasma exchange (PE, 1 plasma volume) before the transplant surgery and receive rATG (Thymoglobuline®) induction (1.5 mg/kg intraoperatively and 1 mg/kg when possible daily within first week up to cumulative dose 5-7 mg/kg) and IVIG 0.5g/kg intravenous infusions, on 1st, 3rd and 5th postoperative day. This is a center standard of care regimen.
Drug: Thymoglobulin
All patients will receive 1.5 mg/kg intraoperatively and 1 mg/kg when possible daily within first week up to cumulative dose 5-7 mg/kg.
Other Names:
  • rATG
Other: Plasma Exchange
All patient will undergo Plasma Exchange before transplantation.
Other Names:
  • PE
Drug: Privigen
Patients randomized to PE/rATG/IVIG group will receive IVIG 0.5g/kg infusions, on 1st, 3rd and 5th postoperative day.
Other Names:
  • IVIG
  • Kiovig

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Combined endpoint defined as biopsy proven antibody mediated changes (Banff 2017, Category 2) and/or TCMR (Banff 2017, Category 4) regardless the biopsy indication (for cause or protocol biopsy) in HLAi (HLA incompatible)kidney transplantation
Time Frame: 12 months
Number of biopsy-confirmed rejections
12 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Incidence of active antibody-mediated rejection (ABMR) lesions within 12 months post-transplantation
Time Frame: 12 months
Number of active active antibody-mediated rejection (ABMR) lesions within 12 months post-transplantation
12 months
Time to active antibody-mediated rejection (ABMR) within 12 months post-transplantation
Time Frame: 12 months
Time to active antibody-mediated rejection (ABMR) occurrence in months
12 months
Incidence of chronic active antibody-mediated rejection (ABMR) and C4d staining without evidence of rejection in protocol biopsies at Month 3 and Month 12
Time Frame: 3 and 12 months
Number of chronic active antibody-mediated rejection (ABMR) and C4d staining without evidence of rejection in protocol biopsies at Month 3 and Month 12
3 and 12 months
Incidence of transplant glomerulopathy (TG) in protocol biopsies at Month 3 and Month 12
Time Frame: 3 and 12 months
Number of biopsies with transplant glomerulopathy
3 and 12 months
Incidence of acute T-cell mediated rejection (TCMR) and chronic active TCMR in protocol biopsies at Month 3 and Month 12 post-transplantation
Time Frame: 3 and 12 months
Number of acute T-cell mediated rejection (TCMR) and chronic active TCMR in protocol biopsies at Month 3 and Month 12
3 and 12 months
Estimated glomerular filtration rate (eGFR) at Month 3, Month 6 and Month 12
Time Frame: 3, 6 and 12 months
Estimated glomerular filtration rate (eGFR) will be assessed at all study visits by CKD-EPI formula.
3, 6 and 12 months
Measured proteinuria and albuminuria at Month 3, Month 6 and Month 12
Time Frame: 3, 6 and 12 months
Proteinuria is defined as ≥ 1 g/l and albuminuria as albumin/creatinine ratio > 3 mg/mmol.
3, 6 and 12 months
Donor specific antibodies (DSA) at Month 3, Month 6 and Month12
Time Frame: 3, 6 and 12 months
Specification of antibodies directed at HLA class I and class II will be performed by LUMINEX method (solid phase assay).
3, 6 and 12 months
De novo donor specific antibodies (DSA) at Month 3, Month 6 and Month 12
Time Frame: 3, 6 and 12 months
Specification of antibodies directed at HLA class I and class II will be performed by LUMINEX method (solid phase assay).
3, 6 and 12 months
Mortality rate within 12 months post-transplantation
Time Frame: 12 months
Number of deaths by any cause anytime during the trial.
12 months
Graft survival (rate of graft loss) within 12 months post transplantation
Time Frame: 12 months
Number graft of graft failures within 12 months
12 months
Incidence of metabolic, malignant and cardiovascular co-morbidities
Time Frame: 12 months
Number of metabolic, malignant and cardiovascular co-morbidities
12 months
Incidence of viral and bacterial complications
Time Frame: 12 months
Number of viral and bacterial complications
12 months
Incidence of BK Virus (BKV), Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) replications detected by PCR (polymerase chain reaction) at Month 3, Month 6 and Month 12
Time Frame: 3, 6 and 12 months
Number of patients with PCR (polymerase chain reaction) positive BK Virus (BKV), Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) replications
3, 6 and 12 months
Incidence of study treatment discontinuation
Time Frame: 12 months
Cessation of trial medication treatment either by the clinician or by the participant himself/herself.
12 months
Incidence of molecular rejection in the 12-month protocol biopsies
Time Frame: 12 months
Number of molecular rejection cases evaluated by the Molecular Microscope Diagnostic System (MMDx) in the 12-month protocol biopsies.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Institute for Clinical and Experimental Medicine

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Ondrej Viklicky, Prof., Institute for Clinical and Experimental Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 27, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 15, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 15, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 4, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 6, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 10, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 15, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 13, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Eudra CT: 2019-003723-37

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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