Hepatorenal SyndromeNCT02123576
Treatment of Type I Hepatorenal Syndrome (HRS) With Pentoxyfylline
A study testing Pentoxyfylline and AMO Therapy in people with Hepatorenal Syndrome, run by Patrick Northup, MD at 1 site in United States.
Trial summary
Pentoxyfylline therapy in addition to the standard of care of albumin, midodrine and octreotide therapy is superior to the standard of care alone in the treatment of Type I hepatorenal syndrome in the first 14 days of hospitalization. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hepatorenal Syndrome
- What is being tested?
- Pentoxyfylline and AMO Therapy
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2014to 31 Dec 2017
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Hospitalized patients with acute or chronic liver disease
- Type I HRS
- Aged greater than or equal to 18
- Non-pregnant
Who cannot join
- Allergy or hypersensitivity to PTX or intolerance to methylxanthines (e.g. caffeine, theophylline)
- Concurrent use of nephrotoxic drugs
- Age less than 18
- Pregnancy
- Uncontrolled bacterial infection
- Renal parenchymal disease (e.g. acute tubular necrosis, glomerular disease, interstitial nephritis and urinary obstruction)
Show all 11Show fewer
- Shock
- TNF alpha antagonist use
- Subject is institutionalized or a prisoner
- Recent cerebral or retinal hemorrhage (contraindication to PTX)
- Severe or poorly controlled cardiovascular disease as determined by the principal investigator to hinder the ability to adhere to study protocols
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Virginia Health System
Charlottesville, Virginia, 22908
About this study
Official title: Treatment of Type I Hepatorenal Syndrome (HRS) With Pentoxyfylline: A Placebo Controlled, Blinded Pilot Study
Pentoxyfylline therapy in addition to the standard of care of albumin, midodrine and octreotide therapy is superior to the standard of care alone in the treatment of Type I hepatorenal syndrome in the first 14 days of hospitalization.
Read the detailed description
Each hospitalized subject will undergo pre-dosing screening with review of his or her history and physical exam from the day of enrollment and safety assessment to ensure no contraindication to use of PTX. Type I HRS will be defined according to the criteria put forth by the American Association for the Study of Liver Disease as (1) cirrhosis with ascites; (2) serum creatinine greater than 1.5 mg/dL; (3) no improvement of serum creatinine (decrease to a level of 1.5 mg/dL or less) after at least two days with diuretic withdrawal and volume expansion with albumin; (4) absence of shock; (5) no current or recent treatment with nephrotoxic drugs; and (6) absence of parenchymal kidney disease as indicated by proteinuria >500 mg/day, microhematuria (>50 red blood cells per high power field), and/or abnormal renal ultrasonography. Baseline testing will be obtained from hospitalization records, including but not limited to chemistry panel, liver function testing, urinalysis, urine electrolytes, coagulation studies, blood cultures, chest x-ray, diagnostic paracentesis, abdominal ultrasound with Doppler.
Subjects will take either placebo three times a day or pentoxyfylline 400mg three times a day or 400mg twice a day for eGFR 10-50 and 400mg once a day for eGFR <10 for 90 days in addition to standard AMO therapy. Treatment will be continued for 14 days unless a study endpoint has been reached at which time either PTX or placebo will be stopped
- Conditions
- Hepatorenal Syndrome
- Being tested
- Pentoxyfylline, Placebo, AMO Therapy
- Keywords
- Hepatorenal syndrome, Renal failure, Pentoxyfylline, Liver transplantation, Cirrhosis
- Medical subject headings
- Hepatorenal Syndrome, Renal Insufficiency, Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PentoxyfyllineDrug
PlaceboDrug
AMO TherapyDrug
Albumin, midodrine and octreotide therapy (standard of care for HRS)
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Pentoxyfylline 400mg three times a day or 400mg twice a day for eGFR 10-50 and 400mg once a day for eGFR <10 for 90 days in addition to standard AMO therapy Receives: Drug: Pentoxyfylline; Drug: AMO Therapy |
| Placebo | Placebo comparator | This is a standard placebo pill. Receives: Drug: Placebo; Drug: AMO Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment Success
We define this as a decrease in serum creatinine level to <1.5 mg/dL without dialysis or death
Measured: 14 days
Secondary outcomes (5)
Change in Serum Creatinine From Baseline
Measured: baseline and 14 days
Incidence of Treatment Failure
Defined as creatinine level above baseline value after day 7, dialysis or death
Measured: up to day 14
Number of Participants With Combined Outcome of Treatment Success and Partial Response
We define as serum creatinine level decreased by >50% from baseline but not to <1.5 mg/dL, without dialysis or HRS recurrence
Measured: 14 days
Transplant Free Survival
Measured: day 30 and 180
Overall Survival
This will be the combination of transplant free survival and those patients who received liver transplant
Measured: up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2014 (estimated)
- Study startApr 2014
- Primary completion31 Dec 2017
- Study completion31 Dec 2017
Why it stopped: Poor enrollment of study population
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Hepatorenal SyndromeStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Patrick Northup, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Patrick Northup, MD, University of Virginia
- Investigators
- Patrick G Northup, MD MHS, Study director, University of VirginiaJonathan G Stine, MD, Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02123576
- Sponsor's protocol ID
- 17365
- Status last verified
- May 2019
- First submitted
- 18 Apr 2014
- Last updated
- 29 May 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Morgan TR, McClain CJ. Pentoxifylline and alcoholic hepatitis. Gastroenterology. 2000 Dec;119(6):1787-91. doi: 10.1053/gast.2000.20826. No abstract available.
PubMed 11113103Angeli P. beta-blockers and refractory ascites in cirrhosis: the message of a team of true scientists. J Hepatol. 2011 Oct;55(4):743-4. doi: 10.1016/j.jhep.2011.02.026. Epub 2011 Mar 10. No abstract available.
PubMed 21396970Lott JP. Renal failure in cirrhosis. N Engl J Med. 2010 Jan 7;362(1):79; author reply 80-1. doi: 10.1056/NEJMc0910190. No abstract available.
PubMed 20054052Spring FA, Dalchau R, Daniels GL, Mallinson G, Judson PA, Parsons SF, Fabre JW, Anstee DJ. The Ina and Inb blood group antigens are located on a glycoprotein of 80,000 MW (the CDw44 glycoprotein) whose expression is influenced by the In(Lu) gene. Immunology. 1988 May;64(1):37-43.
PubMed 2454887Fallon E, Ehrenwald E, Nazarian GK, Smith CI. TIPS with a polytetrafluoroethylene-lined stent graft and associated haemolytic anaemia. Gut. 2008 Aug;57(8):1180-1. No abstract available.
PubMed 18628385
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Type I Hepatorenal Syndrome (HRS) With Pentoxyfylline: A Placebo Controlled, Blinded Pilot Study
- ClinicalTrials.gov ID
- NCT02123576
- Acronym / sponsor ID
- 17365
- Conditions
- Hepatorenal Syndrome
- Keywords
- Hepatorenal syndrome, Renal failure, Pentoxyfylline, Liver transplantation, Cirrhosis
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poor enrollment of study population
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Patrick Northup, MDUniversity, hospital or other
- Study start
- Apr 2014
- Primary completion
- 31 Dec 2017 (actual)
- Study completion
- 31 Dec 2017 (actual)
- First posted
- 25 Apr 2014 (estimated)
- Results
- Posted 29 May 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Pentoxyfylline therapy in addition to the standard of care of albumin, midodrine and octreotide therapy is superior to the standard of care alone in the treatment of Type I hepatorenal syndrome in the first 14 days of hospitalization.
Detailed description
Each hospitalized subject will undergo pre-dosing screening with review of his or her history and physical exam from the day of enrollment and safety assessment to ensure no contraindication to use of PTX. Type I HRS will be defined according to the criteria put forth by the American Association for the Study of Liver Disease as (1) cirrhosis with ascites; (2) serum creatinine greater than 1.5 mg/dL; (3) no improvement of serum creatinine (decrease to a level of 1.5 mg/dL or less) after at least two days with diuretic withdrawal and volume expansion with albumin; (4) absence of shock; (5) no current or recent treatment with nephrotoxic drugs; and (6) absence of parenchymal kidney disease as indicated by proteinuria >500 mg/day, microhematuria (>50 red blood cells per high power field), and/or abnormal renal ultrasonography. Baseline testing will be obtained from hospitalization records, including but not limited to chemistry panel, liver function testing, urinalysis, urine electrolytes, coagulation studies, blood cultures, chest x-ray, diagnostic paracentesis, abdominal ultrasound with Doppler.
Subjects will take either placebo three times a day or pentoxyfylline 400mg three times a day or 400mg twice a day for eGFR 10-50 and 400mg once a day for eGFR <10 for 90 days in addition to standard AMO therapy. Treatment will be continued for 14 days unless a study endpoint has been reached at which time either PTX or placebo will be stopped
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: Pentoxyfylline, Drug: AMO TherapyPentoxyfylline 400mg three times a day or 400mg twice a day for eGFR 10-50 and 400mg once a day for eGFR <10 for 90 days in addition to standard AMO therapy |
| Placebo | Placebo comparator | Drug: Placebo, Drug: AMO TherapyThis is a standard placebo pill. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Hospitalized patients with acute or chronic liver disease
- Type I HRS
- Aged greater than or equal to 18
- Non-pregnant
Key exclusion criteria (11 listed)
- Allergy or hypersensitivity to PTX or intolerance to methylxanthines (e.g. caffeine, theophylline)
- Concurrent use of nephrotoxic drugs
- Age less than 18
- Pregnancy
- Uncontrolled bacterial infection
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 |
|---|---|---|
| Pentoxyfylline | Drug | Treatment |
| Placebo | Drug | Placebo |
| AMO TherapyAlbumin, midodrine and octreotide therapy (standard of care for HRS) | Drug | Placebo, Treatment |
Primary outcome
Number of Participants With Treatment Success
Time frame: 14 days
We define this as a decrease in serum creatinine level to <1.5 mg/dL without dialysis or death
5 secondary outcomes
Change in Serum Creatinine From Baseline
Time frame: baseline and 14 days
Incidence of Treatment Failure
Time frame: up to day 14
Number of Participants With Combined Outcome of Treatment Success and Partial Response
Time frame: 14 days
Transplant Free Survival
Time frame: day 30 and 180
Overall Survival
Time frame: up to 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 11113103Morgan TR, McClain CJ. Pentoxifylline and alcoholic hepatitis. Gastroenterology. 2000 Dec;119(6):1787-91. doi: 10.1053/gast.2000.20826. No abstract available.
- Background: PubMed 21396970Angeli P. beta-blockers and refractory ascites in cirrhosis: the message of a team of true scientists. J Hepatol. 2011 Oct;55(4):743-4. doi: 10.1016/j.jhep.2011.02.026. Epub 2011 Mar 10. No abstract available.
- Background: PubMed 20054052Lott JP. Renal failure in cirrhosis. N Engl J Med. 2010 Jan 7;362(1):79; author reply 80-1. doi: 10.1056/NEJMc0910190. No abstract available.
- Background: PubMed 2454887Spring FA, Dalchau R, Daniels GL, Mallinson G, Judson PA, Parsons SF, Fabre JW, Anstee DJ. The Ina and Inb blood group antigens are located on a glycoprotein of 80,000 MW (the CDw44 glycoprotein) whose expression is influenced by the In(Lu) gene. Immunology. 1988 May;64(1):37-43.
- Background: PubMed 18628385Fallon E, Ehrenwald E, Nazarian GK, Smith CI. TIPS with a polytetrafluoroethylene-lined stent graft and associated haemolytic anaemia. Gut. 2008 Aug;57(8):1180-1. No abstract available.
Related trials for Hepatorenal Syndrome
RecruitingObservational study
Accuracy of Home Lactate Meter and Accu-chek Glucometer in Patients With Glycogen Storage Disease
Glycogen Storage Disease Type IA, Glycogen Storage Disease Type I
RecruitingObservational study
Microbiome and Enteric Signatures in Sepsis-associated Hepatorenal Injury
Sepsis, Acute Kidney Injury Due to Sepsis
RecruitingObservational study
A Retrospective Analysis of Outcomes in Patients With Hepatorenal Syndrome at Methodist Dallas Medical Center
Hepatorenal Syndrome
Active, not recruitingPhase 2
Endothelin Receptor Antagonism With Ambrisentan to Treat Hepatorenal Syndrome
Hepatorenal Syndrome, Liver Cirrhosis
Recruiting
Initial Resuscitation for Acute Kidney Injury in Cirrhosis
Cirrhosis, Liver, Acute Kidney Injury
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.
Patrick G Northup, MD MHS study director
University of Virginia
Jonathan G Stine, MD principal investigator
University of Virginia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Pentoxyfylline and AMO Therapy in people with Hepatorenal Syndrome, run by Patrick Northup, MD at 1 site in United States.
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 11 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: stopped early, as of the sponsor's last update on 29 May 2019. 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 United States. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With Treatment Success (time frame: 14 days). 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 NCT02123576, which also lists 5 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 29 May 2019.