Hepatorenal SyndromeEarly Phase 1NCT02789150
Outcomes of Renal Function in Hepatorenal Syndrome (HRS) Determined By Comparison of Target Mean Arterial Pressure (MAP) of 65 - 70 Mmhg Versus ≥ 85 Mmhg
A Early Phase 1 study testing Norepinephrine (Levophed) in people with Hepatorenal Syndrome, run by University of Louisville at 1 site in United States.
Trial summary
Comparing renal outcomes based on a Mean Arterail Pressure (MAP) of 65-7085mmhg versus a MAP of greater than or equal to 85mmhg Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Hepatorenal Syndrome
- What is being tested?
- Norepinephrine (Levophed)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2015to 11 Jan 2018
- Phase
- Early Phase 1
- 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 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. Admission to intensive care unit (ICU) 2. Age >18 years old 3. Able to obtain informed consent obtained from the patient, from the patient's power of attorney, or from the next of kin 4. Must meet all major criteria based on the International Ascites Club definition and diagnostic criteria for Hepatorenal Syndrome:
- chronic or acute liver disease with advanced hepatic failure and portal hypertension;
- the serum creatinine is greater than 1. 5 mg/dL or 24 hour creatinine clearance of less than 40 ml/min;
- absence of shock, ongoing bacterial infection, and current or recent treatment with nephrotoxic drugs;
- absence of gastrointestinal fluid losses (repeated vomiting or intense diarrhea) or renal fluid losses;
- no sustained improvement in renal function defined as a decrease in serum creatinine to less than 1.5 mg/dL or increase in 24 hour creatinine clearance to 40 ml/min or more following diuretic withdrawal and expansion of plasma volume with 1.5 L of isotonic saline;
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- proteinuria less than 500 mg/dL;
- no ultrasonic evidence of obstructive uropathy or parenchymal renal disease. 5. In addition, patients must meet the definition of HRS type I or HRS type I
- <!-- -->
- -HRS I defined by a rapid deterioration in kidney function with the serum creatinine increasing by more than 100% from baseline to greater than 2.5mg/dl within a two week period.
- -HRS II defined as: patients with refractory ascites with either a steady but moderate degree of functional renal failure (≥ 1.5mg/dl) or deterioration in kidney function that does not fulfill the criteria for HRS type I
Who cannot join
- 1. pre-existing continuous renal replacement therapy cannot or those initiated on dialysis during their hospital stay.
- 2. artificial liver support therapies 3. ongoing gastrointestinal bleeding 4. active surgical issues 5. pre-existing TIPS or TIPS placed during hospital stay 6. long standing hypertension 7. improvement in renal function after central blood volume expansion contraindications to norepinephrine (active myocardial event, ventricular arrhythmia, obstructive physiology, limb ischemia) 8. Pregnancy 9. Treating physicians refusing to enroll patient
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Louisville
Louisville, Kentucky, 40202
About this study
Comparing renal outcomes based on a Mean Arterail Pressure (MAP) of 65-7085mmhg versus a MAP of greater than or equal to 85mmhg
Read the detailed description
Main hypothesis:
The investigators propose that there will be no difference clinical outcomes as evidenced by a significant difference in urine output or change in creatinine between the MAP target ≥ 85mmhg and the MAP target of 65-70 mmhg.
Primary end point:
To determine if High MAP or Low MAP will provide the most optimal renal function. The primary endpoints will be 96h UOP and change in creatinine levels. UOP will be calculated as cc/24 hours. The investigators will compare the change in urinary output of day 1 versus day 4. Creatinine will be measured daily and the change from initiation to completion of the study will be recorded. The mean values of these will be compared.
Secondary end point:
To determine if High MAP or Low MAP will decrease the occurrence of cardiac events (arrhythmias and myocardial infarctions) and vascular events (limb or intestinal ischemia).
Study Design:
This is a prospective, unblinded, randomized, Two-arm treatment, pilot study. Patients will undergo block randomization to receive either a MAP ≥ 85mmhg or a MAP 65-70mmhg.
- Conditions
- Hepatorenal Syndrome
- Being tested
- Norepinephrine (Levophed)
- Medical subject headings
- Hepatorenal Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Norepinephrine (Levophed)Drug
Titrate norepinephrine to MAP 65-70
Norepinephrine (Levophed)Drug
Titrate norepinephrine to MAP 85 or greater
| Study group | Role | What they receive |
|---|---|---|
| MAP 65-70 | Experimental | Goal MAP of 65-70 Receives: Drug: Norepinephrine (Levophed) |
| MAP greater than or equal to 85 | Active comparator | MAP greater than or equal to 85 Receives: Drug: Norepinephrine (Levophed) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Urine output
To determine if High MAP or Low MAP will provide the most optimal renal function. The primary endpoints will be 96h UOP and change in creatinine levels. UOP will be calculated as cc/24 hours. We will compare the change in urinary output of day 1 versus day 4. Creatinine will be measured daily and the change from initiation to completion of the study will be recorded. The mean values of these will be compared.
Measured: 2 years
serum creatinine
Measured: 2 years
Secondary outcomes (2)
Cardiac events
To determine if High MAP or Low MAP will decrease the occurrence of cardiac events (arrhythmias and myocardial infarctions) and vascular events (limb or intestinal ischemia).
Measured: 2 years
ischemic events
To determine if High MAP or Low MAP will decrease the occurrence of cardiac events (arrhythmias and myocardial infarctions) and vascular events (limb or intestinal ischemia).
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2016 (estimated)
- Study startJan 2015
- Primary completion11 Jan 2018
- Study completion11 Jan 2018
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 Hepatorenal SyndromeStudies of the same condition, open and under way.
- More trials run by University of LouisvilleThe sponsor's other registered studies.
- 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Louisville
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mohamed Saad, University of Louisville
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02789150
- Sponsor's protocol ID
- 14.1190
- Status last verified
- Jan 2018
- First submitted
- 28 Jan 2015
- Last updated
- 16 Jan 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Varajic B, Cavallazzi R, Mann J, Furmanek S, Guardiola J, Saad M. High versus low mean arterial pressures in hepatorenal syndrome: A randomized controlled pilot trial. J Crit Care. 2019 Aug;52:186-192. doi: 10.1016/j.jcrc.2019.04.006. Epub 2019 Apr 15.
PubMed 31096099
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Outcomes of Renal Function in Hepatorenal Syndrome (HRS) Determined By Comparison of Target Mean Arterial Pressure (MAP) of 65 - 70 Mmhg Versus ≥ 85 Mmhg
- ClinicalTrials.gov ID
- NCT02789150
- Acronym / sponsor ID
- 14.1190
- Conditions
- Hepatorenal Syndrome
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- University of LouisvilleUniversity, hospital or other
- Study start
- Jan 2015
- Primary completion
- 11 Jan 2018 (actual)
- Study completion
- 11 Jan 2018 (actual)
- First posted
- 2 Jun 2016 (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.
Comparing renal outcomes based on a Mean Arterail Pressure (MAP) of 65-7085mmhg versus a MAP of greater than or equal to 85mmhg
Detailed description
Main hypothesis:
The investigators propose that there will be no difference clinical outcomes as evidenced by a significant difference in urine output or change in creatinine between the MAP target ≥ 85mmhg and the MAP target of 65-70 mmhg.
Primary end point:
To determine if High MAP or Low MAP will provide the most optimal renal function. The primary endpoints will be 96h UOP and change in creatinine levels. UOP will be calculated as cc/24 hours. The investigators will compare the change in urinary output of day 1 versus day 4. Creatinine will be measured daily and the change from initiation to completion of the study will be recorded. The mean values of these will be compared.
Secondary end point:
To determine if High MAP or Low MAP will decrease the occurrence of cardiac events (arrhythmias and myocardial infarctions) and vascular events (limb or intestinal ischemia).
Study Design:
This is a prospective, unblinded, randomized, Two-arm treatment, pilot study. Patients will undergo block randomization to receive either a MAP ≥ 85mmhg or a MAP 65-70mmhg.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MAP 65-70 | Experimental | Drug: Norepinephrine (Levophed)Goal MAP of 65-70 |
| MAP greater than or equal to 85 | Active comparator | Drug: Norepinephrine (Levophed)MAP greater than or equal to 85 |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 1. Admission to intensive care unit (ICU) 2. Age >18 years old 3. Able to obtain informed consent obtained from the patient, from the patient's power of attorney, or from the next of kin 4. Must meet all major criteria based on the International Ascites Club definition and diagnostic criteria for Hepatorenal Syndrome:
- <!-- -->
Key exclusion criteria (2 listed)
- 1. pre-existing continuous renal replacement therapy cannot or those initiated on dialysis during their hospital stay.
- 2. artificial liver support therapies 3. ongoing gastrointestinal bleeding 4. active surgical issues 5. pre-existing TIPS or TIPS placed during hospital stay 6. long standing hypertension 7. improvement in renal function after central blood volume expansion contraindications to norepinephrine (active myocardial event, ventricular arrhythmia, obstructive physiology, limb ischemia) 8. Pregnancy 9. Treating physicians refusing to enroll patient
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 |
|---|---|---|
| Norepinephrine (Levophed)Titrate norepinephrine to MAP 65-70 | Drug | MAP 65-70 |
| Norepinephrine (Levophed)Titrate norepinephrine to MAP 85 or greater | Drug | MAP greater than or equal to 85 |
Primary outcome
Urine output
Time frame: 2 years
To determine if High MAP or Low MAP will provide the most optimal renal function. The primary endpoints will be 96h UOP and change in creatinine levels. UOP will be calculated as cc/24 hours. We will compare the change in urinary output of day 1 versus day 4. Creatinine will be measured daily and the change from initiation to completion of the study will be recorded. The mean values of these will be compared.
serum creatinine
Time frame: 2 years
2 secondary outcomes
Cardiac events
Time frame: 2 years
ischemic events
Time frame: 2 years
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 16 Jan 2018.
- Derived from this study: PubMed 31096099Varajic B, Cavallazzi R, Mann J, Furmanek S, Guardiola J, Saad M. High versus low mean arterial pressures in hepatorenal syndrome: A randomized controlled pilot trial. J Crit Care. 2019 Aug;52:186-192. doi: 10.1016/j.jcrc.2019.04.006. Epub 2019 Apr 15.
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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 Early Phase 1 study testing Norepinephrine (Levophed) in people with Hepatorenal Syndrome, run by University of Louisville 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 11 inclusion and 2 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 16 Jan 2018. 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. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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?
Urine output (time frame: 2 years). The study lists 2 primary outcomes in all. 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 NCT02789150, 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 16 Jan 2018.