Renal InsufficiencyPhase 3ATG_HVHNCT01453218

Safety Use of ATeGe in Liver Transplant Recipients With Pre-transplant Renal Dysfunction

A Phase 3 study testing ATeGe-Fresenius in people with Renal Insufficiency, run by Hospital Vall d'Hebron at 1 site in Spain.

Completed

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

Official record

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Trial summary

Renal dysfunction in the context of liver transplantation is a major issue, with difficult patients' management and determining a worsened prognosis. Physiopathologically pretransplant renal dysfunction is dependent on multifactorial causes, including hypoperfusion-derived functional renal insufficiency, hepatorenal… Read more about this study

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Renal Insufficiency
What is being tested?: ATeGe-Fresenius
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 30 participants
Where: 1 siteSpain
Study dates: Oct 2011to Feb 2020
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

Patients with moderate pre-transplant renal dysfunction as defined serum creatinine levels higher than 1.5 mg/dl or eGFR (MDRD-4) <60ml/min.
First liver transplant, including splits liver transplant.
Patients aged 18-70 years
Without a prior contraindication for protocol biopsy of allograft.

Who cannot join

Multiorgan transplantation and/or liver transplant from DCD and/or with ABO incompatibility.
Uncontrolled concomitant infections (including HIV seropositivity) and/or diarrhoea, vomiting or active gastric ulcer.
Fulminant hepatic insufficiency as first indication for liver transplant
Hemodynamic instability prior to liver transplant.
Recipient presenting present or previous neoplasia, except for non-metastatic basal or squamous cutaneous carcinoma or localized hepatocarcinoma with diameter <5 cm or < 3 known lesions with diameter <3 cm.
Intolerance to study medication.

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Patients having received vaccination with attenuated living vaccines within the previous 4 weeks.
Severe leukopenia (< 1.2 X 10E9/L) and/or thrombocytopenia (< 50x10E9/L) and/or lymphocyte counts (CD2+/CD3+) less than 10 cells/µl.
Significant comorbidity.
Breastfeeding or female patients at fertile age without negative pregnancy test and accepting the use of reliable fertility control method.

Trial locations and contacts

1 site in 1 country.

Spain1 site

Department of HPB Surgery and Transplants, Hospital Vall d´Hebron
Barcelona, 08035

Other trials in Spain

About this study

Official title: Single Centre, Prospective, Open, Non Controlled, Pilot Study for Efficacy and Security Evaluation of Low Nephrotoxicity Immunosuppression, Based on the Use of ATeGe in Liver Transplant Recipients With Pre-transplant Renal Dysfunction

Renal dysfunction in the context of liver transplantation is a major issue, with difficult patients' management and determining a worsened prognosis.

Physiopathologically pretransplant renal dysfunction is dependent on multifactorial causes, including hypoperfusion-derived functional renal insufficiency, hepatorenal syndrome or interstitial parenchymatous insufficiency. On top, intra- or post-transplant events, including hypoperfusion or calcineurin inhibitors nephrotoxicity may aggravate this situation.

At present MELD criteria favours allocation of organs to patients suffering from renal insufficiency, so at least 30% of the investigators liver transplant patients suffer from some degree of renal impairment pretransplant.

After liver transplant impaired renal function tends to recover partially or completely, unless advanced parenchymatous lesions are significantly involved as a major cause of renal dysfunction.

In this context, calcineurin inhibitors avoiding or sparing protocols may help in the recovery from renal insufficiency, improving long-term prognosis. The use of anti-CD25 antibodies is a good option, but provides a limited antirejection prophylaxis, limiting the use of these antibodies to a reduced cohort of liver transplant patients.

Polyclonal antibodies might provide an advantage in management of liver transplant patients with renal insufficiency, without increasing acute rejection episodes of the allograft efficacy and security evaluation of low nephrotoxicity immunosuppression, based on the use of ATeGe, in liver transplant candidates with pre-transplant renal dysfunction.

The aim of this study is to evaluate the efficacy and security use of immunosuppression based on ATeGe in liver transplant recipients with pre-transplant renal dysfunction.

Conditions: Renal Insufficiency
Being tested: ATeGe-Fresenius
Keywords: Renal insufficiency, Liver transplant, Acute rejection, Infections, Hepatitis C recurrence
Medical subject headings: Renal Insufficiency, Infections

What participants receive

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

ATeGe-FreseniusDrug
Administered at 1 , 3, 5 and 7 day post-transplant at 2-3mg/kg with dose adjustment according to CD2/CD3 levels

Study groups in NCT01453218
Study group	Role	What they receive
Basiliximab	No intervention	Historical comparable cohort treated with Basiliximab 20mg iv administered at 0 and 4th day post-transplant
ATeGe-Fresenius	Active comparator	Not described Receives: Drug: ATeGe-Fresenius

What is being measured

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

Renal function improvement after liver transplant
Creatinine (mg/dL) and MDRD Glomerular Filtrate Rate (ml/min/1.73m2) will be measured following the time frame described above
Measured: Measurement will be performed at 1st, 2nd, 3rd, 4th, 5th, 6th, 7th, 14th and 28th day post-transplant, and 2nd, 3rd, 6th and 12th month post-transplant

Secondary outcomes (5)

Incidence of biopsy proven acute cellular rejection.
If liver dysfunction is detected, percutaneous liver biopsy will be performed and histological severity will be assed following BANF criteria
Measured: Evaluation at 1st , 3rd, 6th, 9th and 12th month post-transplant
Patient and graft survival rates after 12 months, causes of death and retransplant
Measured: Evaluation at 1st , 3rd, 6th, 9th and 12th month post-transplant
Relationship between ATeGe doses, immunological variables (lymphocyte counts) and clinical adverse events (acute rejection,infections, HCV recurrence and de novo tumor)
Measured: Evaluation at 1st , 3rd, 6th, 9th and 12th month post-transplant
Incidence and severity of HCV infection recurrence, based on clinical and histological criteria.
Measured: Once liver dysfunction is detected and one year post-transplant by protocol.
Evaluation of metabolic complications (diabetes mellitus, arterial hypertension and dyslipidemia)
Measured: Evaluation at 1st , 3rd, 6th, 9th and 12th month post-transplant

Timeline

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

Oct 2011Feb 2020

First posted17 Oct 2011 (estimated)
Study startOct 2011
Primary completionFeb 2020
Study completionFeb 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (8)Papers the sponsor has linked to this study.
Other trials for Renal InsufficiencyStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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: Basic science
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 30 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01453218
Sponsor's protocol ID: ATG-IRA-HVH.10
Other IDs: 2011-000691-34
Acronym: ATG_HVH
Status last verified: Feb 2020
First submitted: 11 Oct 2011
Last updated: 12 Feb 2020
Results posted: No
Data monitoring committee: No

Publications

Uemura T, Schaefer E, Hollenbeak CS, Khan A, Kadry Z. Outcome of induction immunosuppression for liver transplantation comparing anti-thymocyte globulin, daclizumab, and corticosteroid. Transpl Int. 2011 Jul;24(7):640-50. doi: 10.1111/j.1432-2277.2011.01250.x. Epub 2011 Mar 23.
PubMed 21429047
Benitez CE, Puig-Pey I, Lopez M, Martinez-Llordella M, Lozano JJ, Bohne F, Londono MC, Garcia-Valdecasas JC, Bruguera M, Navasa M, Rimola A, Sanchez-Fueyo A. ATG-Fresenius treatment and low-dose tacrolimus: results of a randomized controlled trial in liver transplantation. Am J Transplant. 2010 Oct;10(10):2296-304. doi: 10.1111/j.1600-6143.2010.03164.x.
PubMed 20883560
Soliman T, Hetz H, Burghuber C, Gyori G, Silberhumer G, Steininger R, Muhlbacher F, Berlakovich GA. Short-term induction therapy with anti-thymocyte globulin and delayed use of calcineurin inhibitors in orthotopic liver transplantation. Liver Transpl. 2007 Jul;13(7):1039-44. doi: 10.1002/lt.21185.
PubMed 17600336
Soliman T, Hetz H, Burghuber C, Gyori G, Silberhumer G, Steininger R, Muhlbacher F, Berlakovich GA. Short-term versus long-term induction therapy with antithymocyte globulin in orthotopic liver transplantation. Transpl Int. 2007 May;20(5):447-52. doi: 10.1111/j.1432-2277.2007.00463.x. Epub 2007 Mar 2.
PubMed 17343686
Kim MJ, Tsinalis D, Franz S, Binet I, Gurke L, Mihatsch MJ, Steiger J, Thiel G, Dickenmann M. ATG-Fresenius or daclizumab induction therapy in immunologically high risk kidney recipients: a prospective randomized pilot trial. Ann Transplant. 2008;13(4):21-7.
PubMed 19034219
Bajjoka I, Hsaiky L, Brown K, Abouljoud M. Preserving renal function in liver transplant recipients with rabbit anti-thymocyte globulin and delayed initiation of calcineurin inhibitors. Liver Transpl. 2008 Jan;14(1):66-72. doi: 10.1002/lt.21309.
PubMed 18161842
Tector AJ, Fridell JA, Mangus RS, Shah A, Milgrom M, Kwo P, Chalasani N, Yoo H, Rouch D, Liangpunsakul S, Herring S, Lumeng L. Promising early results with immunosuppression using rabbit anti-thymocyte globulin and steroids with delayed introduction of tacrolimus in adult liver transplant recipients. Liver Transpl. 2004 Mar;10(3):404-7. doi: 10.1002/lt.20085.
PubMed 15004768
Dopazo C, Charco R, Caralt M, Pando E, Lazaro JL, Gomez-Gavara C, Castells L, Bilbao I. Low Total Dose of Anti-Human T-Lymphocyte Globulin (ATG) Guarantees a Good Glomerular Filtration Rate after Liver Transplant in Recipients with Pretransplant Renal Dysfunction. Can J Gastroenterol Hepatol. 2018 Aug 16;2018:1672621. doi: 10.1155/2018/1672621. eCollection 2018.
PubMed 30186817

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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All Renal Insufficiency trials

Study at a glance

From the registry record, last updated by the sponsor on 12 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Single Centre, Prospective, Open, Non Controlled, Pilot Study for Efficacy and Security Evaluation of Low Nephrotoxicity Immunosuppression, Based on the Use of ATeGe in Liver Transplant Recipients With Pre-transplant Renal Dysfunction
ClinicalTrials.gov ID: NCT01453218
Acronym / sponsor ID: ATG_HVH / ATG-IRA-HVH.10
Conditions: Renal Insufficiency
Keywords: Renal insufficiency, Liver transplant, Acute rejection, Infections, Hepatitis C recurrence
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 30 participants (actual)
Lead sponsor: Hospital Vall d'HebronUniversity, hospital or other
Collaborators: Hospital Universitari Vall d'Hebron Research Institute
Study start: Oct 2011 (actual)
Primary completion: Feb 2020 (actual)
Study completion: Feb 2020 (actual)
First posted: 17 Oct 2011 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Renal dysfunction in the context of liver transplantation is a major issue, with difficult patients' management and determining a worsened prognosis.

After liver transplant impaired renal function tends to recover partially or completely, unless advanced parenchymatous lesions are significantly involved as a major cause of renal dysfunction.

The aim of this study is to evaluate the efficacy and security use of immunosuppression based on ATeGe in liver transplant recipients with pre-transplant renal dysfunction.

Study design

Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Basiliximab	No intervention	–Historical comparable cohort treated with Basiliximab 20mg iv administered at 0 and 4th day post-transplant
ATeGe-Fresenius	Active comparator	Drug: ATeGe-Fresenius

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Patients with moderate pre-transplant renal dysfunction as defined serum creatinine levels higher than 1.5 mg/dl or eGFR (MDRD-4) <60ml/min.
First liver transplant, including splits liver transplant.
Patients aged 18-70 years
Without a prior contraindication for protocol biopsy of allograft.

Key exclusion criteria (10 listed)

Multiorgan transplantation and/or liver transplant from DCD and/or with ABO incompatibility.
Uncontrolled concomitant infections (including HIV seropositivity) and/or diarrhoea, vomiting or active gastric ulcer.
Fulminant hepatic insufficiency as first indication for liver transplant
Hemodynamic instability prior to liver transplant.
Recipient presenting present or previous neoplasia, except for non-metastatic basal or squamous cutaneous carcinoma or localized hepatocarcinoma with diameter <5 cm or < 3 known lesions with diameter <3 cm.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ATeGe-FreseniusAdministered at 1 , 3, 5 and 7 day post-transplant at 2-3mg/kg with dose adjustment according to CD2/CD3 levels	Drug	ATeGe-Fresenius

Primary outcome

Renal function improvement after liver transplant
Time frame: Measurement will be performed at 1st, 2nd, 3rd, 4th, 5th, 6th, 7th, 14th and 28th day post-transplant, and 2nd, 3rd, 6th and 12th month post-transplant
Creatinine (mg/dL) and MDRD Glomerular Filtrate Rate (ml/min/1.73m2) will be measured following the time frame described above

5 secondary outcomes

Incidence of biopsy proven acute cellular rejection.
Time frame: Evaluation at 1st , 3rd, 6th, 9th and 12th month post-transplant
Patient and graft survival rates after 12 months, causes of death and retransplant
Time frame: Evaluation at 1st , 3rd, 6th, 9th and 12th month post-transplant
Relationship between ATeGe doses, immunological variables (lymphocyte counts) and clinical adverse events (acute rejection,infections, HCV recurrence and de novo tumor)
Time frame: Evaluation at 1st , 3rd, 6th, 9th and 12th month post-transplant
Incidence and severity of HCV infection recurrence, based on clinical and histological criteria.
Time frame: Once liver dysfunction is detected and one year post-transplant by protocol.
Evaluation of metabolic complications (diabetes mellitus, arterial hypertension and dyslipidemia)
Time frame: Evaluation at 1st , 3rd, 6th, 9th and 12th month post-transplant

Results and safety

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

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2020.
Background: PubMed 21429047Uemura T, Schaefer E, Hollenbeak CS, Khan A, Kadry Z. Outcome of induction immunosuppression for liver transplantation comparing anti-thymocyte globulin, daclizumab, and corticosteroid. Transpl Int. 2011 Jul;24(7):640-50. doi: 10.1111/j.1432-2277.2011.01250.x. Epub 2011 Mar 23.
Background: PubMed 20883560Benitez CE, Puig-Pey I, Lopez M, Martinez-Llordella M, Lozano JJ, Bohne F, Londono MC, Garcia-Valdecasas JC, Bruguera M, Navasa M, Rimola A, Sanchez-Fueyo A. ATG-Fresenius treatment and low-dose tacrolimus: results of a randomized controlled trial in liver transplantation. Am J Transplant. 2010 Oct;10(10):2296-304. doi: 10.1111/j.1600-6143.2010.03164.x.
Background: PubMed 17600336Soliman T, Hetz H, Burghuber C, Gyori G, Silberhumer G, Steininger R, Muhlbacher F, Berlakovich GA. Short-term induction therapy with anti-thymocyte globulin and delayed use of calcineurin inhibitors in orthotopic liver transplantation. Liver Transpl. 2007 Jul;13(7):1039-44. doi: 10.1002/lt.21185.
Background: PubMed 17343686Soliman T, Hetz H, Burghuber C, Gyori G, Silberhumer G, Steininger R, Muhlbacher F, Berlakovich GA. Short-term versus long-term induction therapy with antithymocyte globulin in orthotopic liver transplantation. Transpl Int. 2007 May;20(5):447-52. doi: 10.1111/j.1432-2277.2007.00463.x. Epub 2007 Mar 2.
Background: PubMed 19034219Kim MJ, Tsinalis D, Franz S, Binet I, Gurke L, Mihatsch MJ, Steiger J, Thiel G, Dickenmann M. ATG-Fresenius or daclizumab induction therapy in immunologically high risk kidney recipients: a prospective randomized pilot trial. Ann Transplant. 2008;13(4):21-7.
Background: PubMed 18161842Bajjoka I, Hsaiky L, Brown K, Abouljoud M. Preserving renal function in liver transplant recipients with rabbit anti-thymocyte globulin and delayed initiation of calcineurin inhibitors. Liver Transpl. 2008 Jan;14(1):66-72. doi: 10.1002/lt.21309.
Background: PubMed 15004768Tector AJ, Fridell JA, Mangus RS, Shah A, Milgrom M, Kwo P, Chalasani N, Yoo H, Rouch D, Liangpunsakul S, Herring S, Lumeng L. Promising early results with immunosuppression using rabbit anti-thymocyte globulin and steroids with delayed introduction of tacrolimus in adult liver transplant recipients. Liver Transpl. 2004 Mar;10(3):404-7. doi: 10.1002/lt.20085.
Derived from this study: PubMed 30186817Dopazo C, Charco R, Caralt M, Pando E, Lazaro JL, Gomez-Gavara C, Castells L, Bilbao I. Low Total Dose of Anti-Human T-Lymphocyte Globulin (ATG) Guarantees a Good Glomerular Filtration Rate after Liver Transplant in Recipients with Pretransplant Renal Dysfunction. Can J Gastroenterol Hepatol. 2018 Aug 16;2018:1672621. doi: 10.1155/2018/1672621. eCollection 2018.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

ITXARONE BILBAO, PhD/MD principal investigator

Department of HPB Surgery and Transplants, Hospital Vall d´Hebron (Barcelona, Spain)

RAMON CHARCO, PHD/MD study director

Department of HPB Surgery and Transplants, Hospital Vall d´Hebron (Barcelona, Spain)

CRISTINA DOPAZO, PhD/MD study chair

Department of HPB Surgery and Transplants, Hospital Vall d´Hebron (Barcelona, Spain)

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing ATeGe-Fresenius in people with Renal Insufficiency, run by Hospital Vall d'Hebron at 1 site in Spain.

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 4 inclusion and 10 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 12 Feb 2020. 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 Spain. 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. 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?

Renal function improvement after liver transplant (time frame: Measurement will be performed at 1st, 2nd, 3rd, 4th, 5th, 6th, 7th, 14th and 28th day post-transplant, and 2nd, 3rd, 6th and 12th month post-transplant). 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 NCT01453218, which also lists 8 linked publications.

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 12 Feb 2020.