Outcomes of Renal Function in Hepatorenal Syndrome (HRS) Determined By Comparison of Target Mean Arterial Pressure (MAP) of 65 - 70 Mmhg Versus ≥ 85 Mmhg

NCT ID: NCT02789150

Last Updated: 2018-01-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-31
• Study Completion Date: 2018-01-11

Brief Summary

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.

Conditions

Hepatorenal Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MAP 65-70

Goal MAP of 65-70

Group Type: EXPERIMENTAL

Norepinephrine (Levophed)

Intervention Type: DRUG

Titrate norepinephrine to MAP 65-70

MAP greater than or equal to 85

MAP greater than or equal to 85

Group Type: ACTIVE_COMPARATOR

Norepinephrine (Levophed)

Intervention Type: DRUG

Titrate norepinephrine to MAP 85 or greater

Interventions

Norepinephrine (Levophed)

Titrate norepinephrine to MAP 65-70

Intervention Type: DRUG

Norepinephrine (Levophed)

Titrate norepinephrine to MAP 85 or greater

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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:

1. chronic or acute liver disease with advanced hepatic failure and portal hypertension;

2. the serum creatinine is greater than 1. 5 mg/dL or 24 hour creatinine clearance of less than 40 ml/min;

3. absence of shock, ongoing bacterial infection, and current or recent treatment with nephrotoxic drugs;

4. absence of gastrointestinal fluid losses (repeated vomiting or intense diarrhea) or renal fluid losses;

5. 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;

6. proteinuria less than 500 mg/dL;

7. 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

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1. -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.

2. -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

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Louisville

OTHER

Sponsor Role: lead

Responsible Party

Mohamed Saad

Associate professor of medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of Louisville

Louisville, Kentucky, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 31096099 (View on PubMed)

Other Identifiers

14.1190

Identifier Type: -

Identifier Source: org_study_id