Outcomes of Renal Function in Hepatorenal Syndrome (HRS) Determined By Comparison of Target Mean Arterial Pressure (MAP) of 65 - 70 Mmhg Versus ≥ 85 Mmhg
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ClinicalTrials.gov Identifier: NCT02789150 |
Recruitment Status :
Completed
First Posted : June 2, 2016
Last Update Posted : January 16, 2018
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Hepatorenal Syndrome | Drug: Norepinephrine (Levophed) | Early Phase 1 |
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 Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 18 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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 |
Study Start Date : | January 2015 |
Actual Primary Completion Date : | January 11, 2018 |
Actual Study Completion Date : | January 11, 2018 |

Arm | Intervention/treatment |
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Experimental: MAP 65-70
Goal MAP of 65-70
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Drug: Norepinephrine (Levophed)
Titrate norepinephrine to MAP 65-70 |
Active Comparator: MAP greater than or equal to 85
MAP greater than or equal to 85
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Drug: Norepinephrine (Levophed)
Titrate norepinephrine to MAP 85 or greater |
- 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 ]
- Cardiac events [ Time Frame: 2 years ]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).
- ischemic events [ Time Frame: 2 years ]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).

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Ages Eligible for Study: | 18 Years to 100 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
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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;
- 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
Exclusion Criteria:
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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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02789150
United States, Kentucky | |
University of Louisville | |
Louisville, Kentucky, United States, 40202 |
Responsible Party: | Mohamed Saad, Associate professor of medicine, University of Louisville |
ClinicalTrials.gov Identifier: | NCT02789150 |
Other Study ID Numbers: |
14.1190 |
First Posted: | June 2, 2016 Key Record Dates |
Last Update Posted: | January 16, 2018 |
Last Verified: | January 2018 |
Hepatorenal Syndrome Syndrome Disease Pathologic Processes Liver Diseases Digestive System Diseases Kidney Diseases Urologic Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Urogenital Diseases Male Urogenital Diseases |
Norepinephrine Adrenergic alpha-Agonists Adrenergic Agonists Adrenergic Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs Sympathomimetics Autonomic Agents Peripheral Nervous System Agents Vasoconstrictor Agents |