CirrhosisPhase 2/3NCT00742339
Terlipressin + Albumin Versus Midodrine + Octreotide in the Treatment of Hepatorenal Syndrome
A Phase 2/3 study testing Terlipressin plus albumin and Midodrine plus octreotide plus human albumin in people with Cirrhosis and Hepatorenal Syndrome, run by University of Padova at 1 site in Italy.
Trial summary
From 1999, several studies have showed that the use of vasoconstrictors in association with albumin are effective in the treatment of hepatorenal syndrome (HRS). The rationale of the use of vasoconstrictors together with albumin in the treatment of this severe complication of portal hypertension in patients with… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Cirrhosis, Hepatorenal Syndrome
- What is being tested?
- Terlipressin plus albumin and Midodrine plus octreotide plus human albumin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 1 siteItaly
- Study dates
- May 2005to Oct 2013
- Phase
- Phase 2/3
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with cirrhosis and diagnosis of HRS type 1 or 2,serum creatinine > 2.5 mg/dl
Who cannot join
- Diagnosis of HCC with a staging beyond the Milan Criteria di Milano
- Septic shock (systolic arterial pressure < 90 mmHg
- Significant heart or respiratory failure
- Peripheral arteriophaty clinically significant
- Previous heart stroke or significant alteration of the ECG
Trial locations and contacts
1 site in 1 country.
Italy1 site
Dept. of Clinical and Experimental Medicine, University of Padova
Padova, 35100
About this study
Official title: Terlipressin + Albumin Versus Midodrine + Octreotide in the Treatment of Hepatorenal Syndrome (HRS): An Open Multicentric Randomized Study
From 1999, several studies have showed that the use of vasoconstrictors in association with albumin are effective in the treatment of hepatorenal syndrome (HRS). The rationale of the use of vasoconstrictors together with albumin in the treatment of this severe complication of portal hypertension in patients with cirrhosis is to correct the reduction of the effective circulating volume due to the splanchnic arterial vasodilatation.In most of these studies terlipressin, a derivate of vasopressin, has been used as vasoconstrictor as intravenous boluses moving from an initial dose of 0.5-1 mg/4 hr. In some studies midodrine, an alpha-adrenergic agonist, given by mouth has been used as vasoconstrictor at a dose ranging from 2.5 up to 12.5 tid together with octreotide, an inhibitor of the release of glucagon, given subcutaneously at a dose ranging from 10 µg upt to 200 µg tid. To the day, there isn't a study comparing terlipressin + albumin versus midodrine + octreotide + albumin in the treatment of HRS in patients with cirrhosis.Thus, the aim of the study is to compare terlipressin + albumin vs midodrine + octreotide + albumin in the treatment of the HRS in patients with cirrhosis.
- Conditions
- Cirrhosis, Hepatorenal Syndrome
- Being tested
- Terlipressin plus albumin, Midodrine plus octreotide plus human albumin
- Keywords
- cirrhosis, hepatorenal syndrome, terlipressin, midodrine, octreotide, human albumin, effective circulating volume, The criteria which will be used for the diagnosis of HRS will be the criteria which were recently published by the International Ascites Club, Patients with cirrhosis and type 2 HRS only with serum creatinine value > 2.5 mg/dl, All patients with cirrhosis and type 1 HRS
- Medical subject headings
- Fibrosis, Hepatorenal Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Terlipressin plus albuminDrug
The terlipressin will be give at the initial dose of 3 mg/24 hours by intravenous continuous infusion. If during the following 48 hours the serum value of creatinine will not change or will go down less than 25%, the dose of terlipressin will be increased to 6 mg/24 hours. If no response will ensue, the dose of terlipressin will be increased to the maximal dose of 12 mg/24 hours. Twenty percent human albumin solution will be administrate together with terlipressin at the dosage of 1 g/Kg of body weight, on first day, and then, to the dosage of 20-40 g/Kg in order to maintain the central venous pressure (CVP) between 10 and 15 cm H2O.The treatment with terlipressin and albumin will be maintained for 24 hours after complete or incomplete resolution. The length of the study in patients with complete and incomplete resolution will reach a maximum of 15 days. In the patients without response the treatment with the high dosage of terlipressin will go on for a maximum of 7 days.
Midodrine plus octreotide plus human albuminDrug
Midodrine will be give orally at the initial dose 7.5 tid together with octreotide at the initial dosage of 100 µg subcutaneously tid. If during the following 96 hours the serum value of creatinine will not change or will go down less than 25%, the dose of midodrine will be increased to 12.5 mg tid Twenty percent human albumin solution will be administrate together with midodrine and octreotide at the dosage of 1 g/Kg of body weight, on first day, and then, to the dosage of 20-40 g/Kg in order to maintain the central venous pressure (CVP) between 10 and 15 cm H2O.The treatment with terlipressin and albumin will be maintained for 24 hours after complete or incomplete resolution. The length of the study in patients with complete and incomplete resolution will reach a maximum of 15 days. In the patients without response the treatment with the high dosage of terlipressin will go on for a maximum of 7 days.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Fifty patients with cirrhosis and HRS will be randomly assigned to arm 1. Receives: Drug: Terlipressin plus albumin |
| 2 | Experimental | Fifty patients with cirrhosis and HRS will be randomly assigned to arm 2. Receives: Drug: Midodrine plus octreotide plus human albumin |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary end-point of the study is the complete reform of the renal function (serum creatinine < 1.5 mg/dl. The primary end point will be evaluated at the end of the treatment.
Measured: The treatment will be continued for a maximum of 15 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2008 (estimated)
- Study startMay 2005
- Primary completionOct 2013
- Study completionOct 2013
Why it stopped: Decision of independent monitoring committee: Risk of non-response to treatment significantly higher in midodrine group than in terlipressin group.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CirrhosisStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Padova
- Sponsor type
- University, hospital or other
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00742339
- Sponsor's protocol ID
- 1264P
- Status last verified
- Oct 2014
- First submitted
- 26 Aug 2008
- Last updated
- 15 Oct 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Salerno F, Gerbes A, Gines P, Wong F, Arroyo V. Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis. Gut. 2007 Sep;56(9):1310-8. doi: 10.1136/gut.2006.107789. Epub 2007 Mar 27. No abstract available.
PubMed 17389705
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Terlipressin + Albumin Versus Midodrine + Octreotide in the Treatment of Hepatorenal Syndrome (HRS): An Open Multicentric Randomized Study
- ClinicalTrials.gov ID
- NCT00742339
- Acronym / sponsor ID
- 1264P
- Conditions
- Cirrhosis, Hepatorenal Syndrome
- Keywords
- cirrhosis, hepatorenal syndrome, terlipressin, midodrine, octreotide, human albumin, effective circulating volume, The criteria which will be used for the diagnosis of HRS will be the criteria which were recently published by the International Ascites Club
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Decision of independent monitoring committee: Risk of non-response to treatment significantly higher in midodrine group than in terlipressin group.
- Enrolment
- 49 participants (actual)
- Lead sponsor
- University of PadovaUniversity, hospital or other
- Study start
- May 2005
- Primary completion
- Oct 2013 (actual)
- Study completion
- Oct 2013 (actual)
- First posted
- 27 Aug 2008 (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.
From 1999, several studies have showed that the use of vasoconstrictors in association with albumin are effective in the treatment of hepatorenal syndrome (HRS). The rationale of the use of vasoconstrictors together with albumin in the treatment of this severe complication of portal hypertension in patients with cirrhosis is to correct the reduction of the effective circulating volume due to the splanchnic arterial vasodilatation.In most of these studies terlipressin, a derivate of vasopressin, has been used as vasoconstrictor as intravenous boluses moving from an initial dose of 0.5-1 mg/4 hr. In some studies midodrine, an alpha-adrenergic agonist, given by mouth has been used as vasoconstrictor at a dose ranging from 2.5 up to 12.5 tid together with octreotide, an inhibitor of the release of glucagon, given subcutaneously at a dose ranging from 10 µg upt to 200 µg tid. To the day, there isn't a study comparing terlipressin + albumin versus midodrine + octreotide + albumin in the treatment of HRS in patients with cirrhosis.Thus, the aim of the study is to compare terlipressin + albumin vs midodrine + octreotide + albumin in the treatment of the HRS in patients with cirrhosis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: Terlipressin plus albuminFifty patients with cirrhosis and HRS will be randomly assigned to arm 1. |
| 2 | Experimental | Drug: Midodrine plus octreotide plus human albuminFifty patients with cirrhosis and HRS will be randomly assigned to arm 2. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients with cirrhosis and diagnosis of HRS type 1 or 2,serum creatinine > 2.5 mg/dl
Key exclusion criteria (5 listed)
- Diagnosis of HCC with a staging beyond the Milan Criteria di Milano
- Septic shock (systolic arterial pressure < 90 mmHg
- Significant heart or respiratory failure
- Peripheral arteriophaty clinically significant
- Previous heart stroke or significant alteration of the ECG
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 |
|---|---|---|
| Terlipressin plus albuminThe terlipressin will be give at the initial dose of 3 mg/24 hours by intravenous continuous infusion. If during the following 48 hours the serum value of creatinine will not change or will go down less than 25%, the dose of terlipressin will be increased to 6 mg/24 hours. If no response will ensue, the dose of terlipressin will be increased to the maximal dose of 12 mg/24 hours. Twenty percent human albumin solution will be administrate together with terlipressin at the dosage of 1 g/Kg of body weight, on first day, and then, to the dosage of 20-40 g/Kg in order to maintain the central venous pressure (CVP) between 10 and 15 cm H2O.The treatment with terlipressin and albumin will be maintained for 24 hours after complete or incomplete resolution. The length of the study in patients with complete and incomplete resolution will reach a maximum of 15 days. In the patients without response the treatment with the high dosage of terlipressin will go on for a maximum of 7 days. | Drug | 1 |
| Midodrine plus octreotide plus human albuminMidodrine will be give orally at the initial dose 7.5 tid together with octreotide at the initial dosage of 100 µg subcutaneously tid. If during the following 96 hours the serum value of creatinine will not change or will go down less than 25%, the dose of midodrine will be increased to 12.5 mg tid Twenty percent human albumin solution will be administrate together with midodrine and octreotide at the dosage of 1 g/Kg of body weight, on first day, and then, to the dosage of 20-40 g/Kg in order to maintain the central venous pressure (CVP) between 10 and 15 cm H2O.The treatment with terlipressin and albumin will be maintained for 24 hours after complete or incomplete resolution. The length of the study in patients with complete and incomplete resolution will reach a maximum of 15 days. In the patients without response the treatment with the high dosage of terlipressin will go on for a maximum of 7 days. | Drug | 2 |
Primary outcome
The primary end-point of the study is the complete reform of the renal function (serum creatinine < 1.5 mg/dl. The primary end point will be evaluated at the end of the treatment.
Time frame: The treatment will be continued for a maximum of 15 days
Results and safety
The study was stopped early (reason given: Decision of independent monitoring committee: Risk of non-response to treatment significantly higher in midodrine group than in terlipressin group.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2014.
- Background: PubMed 17389705Salerno F, Gerbes A, Gines P, Wong F, Arroyo V. Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis. Gut. 2007 Sep;56(9):1310-8. doi: 10.1136/gut.2006.107789. Epub 2007 Mar 27. No abstract available.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Terlipressin plus albumin and Midodrine plus octreotide plus human albumin in people with Cirrhosis and Hepatorenal Syndrome, run by University of Padova at 1 site in Italy.
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 1 inclusion and 5 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 15 Oct 2014. 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 Italy. 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 was stopped early (reason given: Decision of independent monitoring committee: Risk of non-response to treatment significantly higher in midodrine group than in terlipressin group.). Results are not available in the source record.
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?
The primary end-point of the study is the complete reform of the renal function (serum creatinine < 1.5 mg/dl. The primary end point will be evaluated at the end of the treatment. (time frame: The treatment will be continued for a maximum of 15 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 NCT00742339, 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 Oct 2014.