Droxidopa to Increase Mean Arterial Pressure in Decompensated Cirrhosis Patients With Acute Kidney Injury
Giuseppe Cullaro, MD
Summary
This study tests whether a medication called droxidopa can help improve blood flow to the kidneys in people with liver cirrhosis who develop kidney problems while in the hospital. When someone with cirrhosis experiences kidney injury, having better blood pressure can help their kidneys recover. Droxidopa is an oral medication that may help raise blood pressure without requiring intensive care or invasive treatments. The study will compare droxidopa to a placebo (inactive pill) in 75 people hospitalized with cirrhosis and kidney injury. Participants will take either droxidopa or placebo pills for 28 days and be monitored for an additional 30 days. Researchers will measure changes in blood pressure and kidney function to determine if droxidopa is effective and safe for these patients. This research could identify a new treatment option for a serious complication of liver disease.
Description
Acute kidney injury (AKI) occurs in up to 50% of hospitalized patients with decompensated cirrhosis and carries mortality rates exceeding 50%. Recent evidence indicates that progression of AKI after initial diagnosis significantly impacts outcomes, with patients whose AKI worsens having up to 8 times higher mortality compared to those without progression. Mean arterial pressure (MAP) appears to be a key mediator of kidney function and recovery in cirrhosis. Multiple studies have established that each 5 mmHg increase in MAP is associated with a 1.07-1.19 times greater likelihood of AKI recover…
Eligibility
- Age range
- 18–70 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Ability to provide informed consent by subject or legally authorized representative * Consent to blood and urine collection for biomarker analysis * Ability to take oral medications * At least 18 years of age * Hospitalized at Columbia University Irving Medical Center * Child-Pugh Score ≥ B7 cirrhosis (documented by imaging, biopsy, or clinical evidence) * KDIGO Stage 1 AKI or greater, defined as: * ≥0.3 mg/dL increase in serum creatinine within 48 hours OR * ≥50% increase in serum creatinine from outpatient baseline * Mean arterial pressure ≤85 mmHg averaged over 24 hou…
Interventions
- DrugDroxidopa capsules
Droxidopa is an oral synthetic amino acid that is directly metabolized to norepinephrine by dopa-decarboxylase. It will be administered at an initial dose of 100 mg three times daily, titrated in 100 mg increments every 24 hours based on blood pressure response, up to a maximum of 300 mg three times daily. Doses will be given approximately 4 hours apart during daytime hours, at least 3 hours apart, with a maximum total daily dose of 900 mg. The treatment duration is 28 days. The drug will be over-encapsulated using opaque capsules to maintain the double-blind design.
- OtherPlacebo
Matching placebo capsules containing microcrystalline cellulose (from Millipore Sigma) will be over-encapsulated using identical opaque capsules to maintain blinding. Placebo will be administered following the same schedule as the active treatment: three times daily with the same titration protocol based on blood pressure response, for a treatment duration of 28 days. The Columbia University Research Pharmacy will perform over-encapsulation of both active drug and placebo to ensure they are identical in appearance.
Location
- Columbia University Irving Medical CenterNew York, New York