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Alcoholic HepatitisPhase 3CorpentoxHAANCT01214226

Double-blind Randomized Controlled Trial in Severe Alcoholic Hepatitis

A Phase 3 study testing Pentoxifylline in people with Alcoholic Hepatitis and Alcoholic Liver Disease, run by University Hospital, Lille at 28 sites in 2 countries.

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

The treatment of severe forms of alcoholic hepatitis (AH) constitutes a major challenge for clinicians involved in the management of severe alcoholic liver disease. In patients with Maddrey function higher than 32, compelling evidence from data has shown that corticosteroids improve short-term survival. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Alcoholic Hepatitis, Alcoholic Liver Disease
What is being tested?
Pentoxifylline
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
278 participants
Where
28 sitesin 2 countries
Study dates
Dec 2007to Jan 2011
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

  • Alcohol consumption more than 40 gram/day for women and 50 gram/day for men
  • Maddrey discriminant function higher than 32
  • Onset of jaundice within the 3 previous months
  • Biopsy-proven alcoholic hepatitis

Who cannot join

  • Hypersensitivity to pentoxifylline
  • Any severe disease that may potential affect survival such as cardiac failure, ischemic cardiopathy, respiratory failure
  • Any neoplasm that occurred within the 2 previous years
  • Hepatocellular carcinoma or any previous diagnosis of hepatocellular carcinoma
  • Portal thrombosis
  • Severe gastrointestinal bleeding
Show all 16Show fewer
  • Uncontrolled sepsis within the 7 previous days
  • Hepatorenal syndrome type I
  • Viral and fungal infection
  • Acute pancreatitis
  • Any tuberculosis that occurred within the 5 previous years
  • Psychiatric disorders that contraindicate the use of corticosteroids
  • Infection related to virus of the hepatites B or C
  • HIV infection (Human immunodeficiency virus)
  • Any treatment with corticosteroids, immunosuppressive agents, budesonide, thalidomide or pentoxifylline that was given within the previous year
  • Pregnancy or breast feeding

Trial locations and contacts

28 sites in 2 countries.

28 sites in 2 countries

France27 sites

  • University hospital

    Angers, 49933

  • Centre hospitalier

    Béthune, 62408

  • Hôpital Jean Verdier (AH-HP)

    Bondy, 93143

  • University hospital

    Bordeaux, 33000

  • University hospital

    Caen, 14000

  • Hospital Antoine Béclère (Assistance Publique des Hôpiaux de Paris)

    Clamart, 92141

  • Hôpital Beaujon (AH-HP)

    Clichy, 92118

  • Centre Hospitalier

    Creil, 60100

  • Hôpital Henri Mondor (AP-HP)

    Créteil, 94000

  • Centre hospitalier

    Dunkirk, 59240

  • Centre Hospitalier

    Lens, 62300

  • University hospital

    Lille, 59037

  • Centre hospitalier Sambre en avesnois

    Maubeuge, 59600

  • University hospital

    Montpellier, 34295

  • University hospital

    Nantes, 45000

  • University hospital

    Nice, 06202

  • Hôpital Saint Antoine (AP-HP)

    Paris, 75012

  • Hôpital de la Pitié-Salpétrière (AP-HP)

    Paris, 75013

  • Hôpital Cochin (AH-HP)

    Paris, 75014

  • University hospital

    Poitiers, 49000

  • University hospital

    Rennes, 35033

  • Centre Hospitalier Victor Provo

    Roubaix, 59100

  • University Hospital

    Strasbourg, 67100

  • Centre Hospitalier

    Tourcoing, 59208

  • Centre Hospitalier

    Valenciennes, 59300

  • University hospital, Nancy

    Vandœuvre-lès-Nancy, 54511

  • Hôpital Paul Brousse (AH-HP)

    Villejuif, 94000

Other trials in France

Belgium1 site

  • University hospital

    Brussels, 1070

Other trials in Belgium

About this study

Official title: Evaluation of the Survival Benefit of the Adjunction of Pentoxifylline to Corticosteroids in Patients Suffering From Severe Alcoholic Hepatitis

The treatment of severe forms of alcoholic hepatitis (AH) constitutes a major challenge for clinicians involved in the management of severe alcoholic liver disease. In patients with Maddrey function higher than 32, compelling evidence from data has shown that corticosteroids improve short-term survival. However, novel strategies or molecules are required in light of the fact that approximately 40 % of patients continue to die at 6 months. A double-blinded randomized controlled trial of 101 patients has showed that Pentoxifylline improves survival of patients with severe AH, as compared to placebo. In terms of mechanisms, the effect of pentoxifylline is related to prevention of hepatorenal function whereas corticosteroids induce an early improvement in liver function. When considering these differences of mechanisms, many clinicians suggest that the addition of pentoxyfilline to corticosteroids is an attractive option that needs to be tested in patients with severe AH.

Read the detailed description

The aim of the present study is to determine whether or not the adjunction of Pentoxifylline to corticosteroids would improve 6-month survival of patients with severe alcoholic hepatitis. This multicenter, randomized, double-blinded, controlled, phase 3 trial was conducted in 24 centers located in France and Belgium. Alcoholic hepatitis was biopsy-proven. All eligible patients were randomly assigned in a 1:1 ratio to receive corticosteroids + Pentoxifylline or corticosteroids + Placebo. The primary outcome of the study was 6-month survival. Assuming a two-sided type I error of 0.05, a randomization ratio of 1:1 between the 2 groups, 6-month survival of 64% in the Placebo and Corticosteroids group and of 78 % in the Pentoxifylline and Corticosteroids group, we estimated that with 268 randomized patients (134 in each group), the study would have a power of 80% to detect this increase in 6-month survival in the Pentoxifylline and Corticosteroid group.

Being tested
Pentoxifylline, placebo
Medical subject headings
Hepatitis, Alcoholic, Liver Diseases, Alcoholic

What participants receive

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

  • PentoxifyllineDrug

    Also called TORENTAL 400MG

    400 mg prolonged-released tablets 3 time per day for 1 month.

  • placeboDrug

    prolonged-release tablets 3 time per day for 1 month

Study groups in NCT01214226
Study groupRoleWhat they receive
Pentoxifylline + PrednisoloneActive comparatorPentoxifylline 400 mg prolonged-released tablets 3 time a day [1200 mg/day] + Prednisolone 2 ORODISPERSIBLE TABLETS OF 20 MG 1 TIME PER DAY [40 mg/day]
Receives: Drug: placebo
Placebo + PrednisolonePlacebo comparatorPlacebo prolonged-release tabled 3 time a day + Prednisolone 2 ORODISPERSIBLE TABLETS OF 20 MG 1 TIME PER DAY [40 mg/day]
Receives: Drug: Pentoxifylline

What is being measured

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

  1. Overall Survival

    Measured: 6 months

Secondary outcomes (3)

  1. Hepatorenal syndrome

    Measured: 6 months

  2. Score of Lille model

    Measured: Seven days

  3. Percentage of Meld score (Model for End-stage Liver Disease) higher than 17

    Measured: 6 months

Timeline

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

  1. First posted4 Oct 2010 (estimated)
  2. Study startDec 2007
  3. Primary completionDec 2010
  4. Study completionJan 2011

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
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
278 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01214226
Sponsor's protocol ID
2006-006944-78
Other IDs
PROM 2006/0636, 2006-006944-78
Acronym
CorpentoxHAA
Status last verified
Sep 2010
First submitted
1 Oct 2010
Last updated
1 Jun 2011
Results posted
No
Data monitoring committee
No

Publications

  • Lucey MR, Mathurin P, Morgan TR. Alcoholic hepatitis. N Engl J Med. 2009 Jun 25;360(26):2758-69. doi: 10.1056/NEJMra0805786. No abstract available.

    PubMed 19553649

  • Louvet A, Wartel F, Castel H, Dharancy S, Hollebecque A, Canva-Delcambre V, Deltenre P, Mathurin P. Infection in patients with severe alcoholic hepatitis treated with steroids: early response to therapy is the key factor. Gastroenterology. 2009 Aug;137(2):541-8. doi: 10.1053/j.gastro.2009.04.062. Epub 2009 May 13.

    PubMed 19445945

  • Louvet A, Naveau S, Abdelnour M, Ramond MJ, Diaz E, Fartoux L, Dharancy S, Texier F, Hollebecque A, Serfaty L, Boleslawski E, Deltenre P, Canva V, Pruvot FR, Mathurin P. The Lille model: a new tool for therapeutic strategy in patients with severe alcoholic hepatitis treated with steroids. Hepatology. 2007 Jun;45(6):1348-54. doi: 10.1002/hep.21607.

    PubMed 17518367

  • Mathurin P. Corticosteroids for alcoholic hepatitis--what's next? J Hepatol. 2005 Sep;43(3):526-33. doi: 10.1016/j.jhep.2005.06.003. No abstract available.

    PubMed 16026887

  • Naveau S, Chollet-Martin S, Dharancy S, Mathurin P, Jouet P, Piquet MA, Davion T, Oberti F, Broet P, Emilie D; Foie-Alcool group of the Association Francaise pour l'Etude du Foie. A double-blind randomized controlled trial of infliximab associated with prednisolone in acute alcoholic hepatitis. Hepatology. 2004 May;39(5):1390-7. doi: 10.1002/hep.20206.

    PubMed 15122768

  • Mathurin P, Abdelnour M, Ramond MJ, Carbonell N, Fartoux L, Serfaty L, Valla D, Poupon R, Chaput JC, Naveau S. Early change in bilirubin levels is an important prognostic factor in severe alcoholic hepatitis treated with prednisolone. Hepatology. 2003 Dec;38(6):1363-9. doi: 10.1016/j.hep.2003.09.038.

    PubMed 14647046

  • Mathurin P, Mendenhall CL, Carithers RL Jr, Ramond MJ, Maddrey WC, Garstide P, Rueff B, Naveau S, Chaput JC, Poynard T. Corticosteroids improve short-term survival in patients with severe alcoholic hepatitis (AH): individual data analysis of the last three randomized placebo controlled double blind trials of corticosteroids in severe AH. J Hepatol. 2002 Apr;36(4):480-7. doi: 10.1016/s0168-8278(01)00289-6.

    PubMed 11943418

  • Mathurin P, Duchatelle V, Ramond MJ, Degott C, Bedossa P, Erlinger S, Benhamou JP, Chaput JC, Rueff B, Poynard T. Survival and prognostic factors in patients with severe alcoholic hepatitis treated with prednisolone. Gastroenterology. 1996 Jun;110(6):1847-53. doi: 10.1053/gast.1996.v110.pm8964410.

    PubMed 8964410

  • Ramond MJ, Poynard T, Rueff B, Mathurin P, Theodore C, Chaput JC, Benhamou JP. A randomized trial of prednisolone in patients with severe alcoholic hepatitis. N Engl J Med. 1992 Feb 20;326(8):507-12. doi: 10.1056/NEJM199202203260802.

    PubMed 1531090

  • Mathurin P, Louvet A, Duhamel A, Nahon P, Carbonell N, Boursier J, Anty R, Diaz E, Thabut D, Moirand R, Lebrec D, Moreno C, Talbodec N, Paupard T, Naveau S, Silvain C, Pageaux GP, Sobesky R, Canva-Delcambre V, Dharancy S, Salleron J, Dao T. Prednisolone with vs without pentoxifylline and survival of patients with severe alcoholic hepatitis: a randomized clinical trial. JAMA. 2013 Sep 11;310(10):1033-41. doi: 10.1001/jama.2013.276300.

    PubMed 24026598

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Pentoxifylline in people with Alcoholic Hepatitis and Alcoholic Liver Disease, run by University Hospital, Lille at 28 sites in 2 countries.

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 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 1 Jun 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 28 sites in France, Belgium. 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?

Overall Survival (time frame: 6 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 NCT01214226, which also lists 10 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 1 Jun 2011.

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