AzTrials
AzTrials

Kidney TransplantationPhase 3INHIBITNCT04302805

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

A Phase 3 study testing Privigen, Thymoglobulin and Plasma Exchange in people with Kidney Transplantation, run by Institute for Clinical and Experimental Medicine at 1 site in Czechia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Kidney Transplantation
What is being tested?
Privigen, Thymoglobulin and Plasma Exchange
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
17 participants
Where
1 siteCzechia
Study dates
27 Jul 2020to 15 Jun 2024
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)

Who cannot join

  • 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
Show all 16Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

Czechia1 site

  • Institute for Clinical and Experimental Medicine

    Prague, 140 21

Other trials in Czechia

About this study

Official title: 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.

Read the 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.

Being tested
Privigen, Thymoglobulin, Plasma Exchange
Keywords
Antibody-mediated rejection, Intravenous immunoglobulin, Rabbit Anti-thymocyte Globulin, Donor specific antibodies

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PrivigenDrug

    Also called IVIG, Kiovig

    Patients randomized to PE/rATG/IVIG group will receive IVIG 0.5g/kg infusions, on 1st, 3rd and 5th postoperative day.

  • ThymoglobulinDrug

    Also called rATG

    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.

  • Plasma ExchangeOther

    Also called PE

    All patient will undergo Plasma Exchange before transplantation.

Study groups in NCT04302805
Study groupRoleWhat they receive
PE/rATGPlacebo comparatorStudy 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).
Receives: Drug: Thymoglobulin; Other: Plasma Exchange
PE/rATG/IVIGActive comparatorStudy 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.
Receives: Drug: Privigen; Drug: Thymoglobulin; Other: Plasma Exchange

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Number of biopsy-confirmed rejections

    Measured: 12 months

Secondary outcomes (16)

  1. Incidence of active antibody-mediated rejection (ABMR) lesions within 12 months post-transplantation

    Number of active active antibody-mediated rejection (ABMR) lesions within 12 months post-transplantation

    Measured: 12 months

  2. Time to active antibody-mediated rejection (ABMR) within 12 months post-transplantation

    Time to active antibody-mediated rejection (ABMR) occurrence in months

    Measured: 12 months

  3. Incidence of chronic active antibody-mediated rejection (ABMR) and C4d staining without evidence of rejection in protocol biopsies at Month 3 and Month 12

    Number of chronic active antibody-mediated rejection (ABMR) and C4d staining without evidence of rejection in protocol biopsies at Month 3 and Month 12

    Measured: 3 and 12 months

  4. Incidence of transplant glomerulopathy (TG) in protocol biopsies at Month 3 and Month 12

    Number of biopsies with transplant glomerulopathy

    Measured: 3 and 12 months

  5. Incidence of acute T-cell mediated rejection (TCMR) and chronic active TCMR in protocol biopsies at Month 3 and Month 12 post-transplantation

    Number of acute T-cell mediated rejection (TCMR) and chronic active TCMR in protocol biopsies at Month 3 and Month 12

    Measured: 3 and 12 months

  6. Estimated glomerular filtration rate (eGFR) at Month 3, Month 6 and Month 12

    Estimated glomerular filtration rate (eGFR) will be assessed at all study visits by CKD-EPI formula.

    Measured: 3, 6 and 12 months

  7. Measured proteinuria and albuminuria at Month 3, Month 6 and Month 12

    Proteinuria is defined as ≥ 1 g/l and albuminuria as albumin/creatinine ratio > 3 mg/mmol.

    Measured: 3, 6 and 12 months

  8. Donor specific antibodies (DSA) at Month 3, Month 6 and Month12

    Specification of antibodies directed at HLA class I and class II will be performed by LUMINEX method (solid phase assay).

    Measured: 3, 6 and 12 months

  9. De novo donor specific antibodies (DSA) at Month 3, Month 6 and Month 12

    Specification of antibodies directed at HLA class I and class II will be performed by LUMINEX method (solid phase assay).

    Measured: 3, 6 and 12 months

  10. Mortality rate within 12 months post-transplantation

    Number of deaths by any cause anytime during the trial.

    Measured: 12 months

  11. Graft survival (rate of graft loss) within 12 months post transplantation

    Number graft of graft failures within 12 months

    Measured: 12 months

  12. Incidence of metabolic, malignant and cardiovascular co-morbidities

    Number of metabolic, malignant and cardiovascular co-morbidities

    Measured: 12 months

  13. Incidence of viral and bacterial complications

    Number of viral and bacterial complications

    Measured: 12 months

  14. 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

    Number of patients with PCR (polymerase chain reaction) positive BK Virus (BKV), Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) replications

    Measured: 3, 6 and 12 months

  15. Incidence of study treatment discontinuation

    Cessation of trial medication treatment either by the clinician or by the participant himself/herself.

    Measured: 12 months

  16. Incidence of molecular rejection in the 12-month protocol biopsies

    Number of molecular rejection cases evaluated by the Molecular Microscope Diagnostic System (MMDx) in the 12-month protocol biopsies.

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Mar 2020
  2. Study start27 Jul 2020
  3. Primary completion15 Apr 2024
  4. Study completion15 Jun 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Model description
The present study is a prospective randomized single-centre open-label two-arm Phase III.b non-inferiority clinical trial. This trial aims to prove similar efficacy of PE/rATG 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.
Masking
None (open label)
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04302805
Sponsor's protocol ID
Eudra CT: 2019-003723-37
Acronym
INHIBIT
Status last verified
Aug 2024
First submitted
4 Mar 2020
Last updated
15 Aug 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Viklicky O, Zahradka I, Mares J, Slatinska J, Parikova A, Petr V, Roder M, Jaklova K, Osickova K, Janousek L, Hruba P. 12-Month Outcomes of a Prospective Randomized Trial Investigating Effects of IVIG on Top of rATG Versus rATG Alone in Pre-Sensitized Kidney Transplant Recipients: The INHIBIT Study. Transpl Int. 2025 May 19;38:14312. doi: 10.3389/ti.2025.14312. eCollection 2025.

    PubMed 40458542

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Privigen, Thymoglobulin and Plasma Exchange in people with Kidney Transplantation, run by Institute for Clinical and Experimental Medicine at 1 site in Czechia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Czechia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04302805, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Aug 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in