Droxidopa to Increase Mean Arterial Pressure in Decompensated Cirrhosis Patients With Acute Kidney Injury

NCT06937307 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: AAAV7484
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Acute Kidney Injury; Cirrhosis; Decompensated Cirrhosis of Liver

Keywords

Acute Kidney Injury; Cirrhosis; Decompensated Cirrhosis

Outcome Measures

Primary Outcomes (1)

• Change in mean arterial pressure (MAP)

  The difference in mean arterial pressure between treatment groups over the 28-day treatment period, assessed using a linear mixed-effects model with fixed effects for treatment group and time, plus their interaction, while accounting for between-subject variability through random intercepts.

  Baseline to 28 days

Secondary Outcomes (3)

• Change in serum creatinine

  28 days

• All-cause mortality

  58 days

• Liver transplantation

  58 days

Study Arms (2)

Droxidopa

EXPERIMENTAL

Participants in this arm will receive oral droxidopa capsules at an initial dose of 100 mg three times daily, titrated in 100 mg increments every 24 hours based on blood pressure response and tolerability, up to a maximum dose of 300 mg three times daily. Doses will be given approximately 4 hours apart during daytime hours for a total treatment duration of 28 days.

Drug: Droxidopa capsules

Placebo

PLACEBO COMPARATOR

Participants in this arm will receive matched placebo capsules following the same dosing schedule and titration protocol as the experimental arm. Placebo capsules will be identical in appearance to droxidopa capsules with the same over-encapsulation process to maintain blinding. Doses will be given three times daily for a total treatment duration of 28 days.

Other: Placebo

Interventions

Droxidopa capsules DRUG

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.

Also known as: L-threo-3,4-dihydroxyphenylserine

Droxidopa

Placebo OTHER

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.

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 hours prior to randomization
• For women of childbearing potential: negative pregnancy test and agreement to use effective contraception

You may not qualify if:

• Serum creatinine \>4.0 mg/dL or current renal replacement therapy
• Age \>70 years
• Severe cardiovascular disease, including:
• Unstable angina
• Congestive heart failure requiring escalating medical therapy
• Symptomatic peripheral vascular disease
• Any cardiovascular condition deemed severe by investigator
• Active gastrointestinal bleeding, defined as requiring ≥ 2 units of packed red blood cells during the screening period
• Acute respiratory failure requiring more than 6L of Nasal Canula
• Use of medications that could interact with droxidopa including:
• MAOI inhibitors
• Norepinephrine reuptake inhibitors
• Other investigational drugs
• Pregnancy or breastfeeding
• Any episode of a SBP ≥ 180 mmHg or a DBP ≥ 120 mmHg on two measurements, 1 minute apart

Sponsors & Collaborators

• Giuseppe Cullaro, MD: lead

Study Sites (1)

Columbia University Irving Medical Center

New York, New York, 10032, United States

RECRUITING

MeSH Terms

Conditions

Acute Kidney Injury; Fibrosis

Interventions

Droxidopa; 3,4-dihydroxyphenylserine aldolase

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Norepinephrine; Catecholamines; Amines; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Serine; Amino Acids, Neutral; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Giuseppe Cullaro, MD, MAS

  Columbia University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Giuseppe Cullaro, MD, MAS

CONTACT

2123050914; gc2576@cumc.columbia.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a double-blind, placebo-controlled study in which both active drug (droxidopa) and placebo will be over-encapsulated using identical opaque capsules by the Columbia University Research Pharmacy. Only the Research Pharmacy staff will be unblinded to enable proper preparation and dispensing of study medication, while all participants, investigators, care providers, and outcomes assessors will remain blinded to treatment assignment. Emergency unblinding procedures are available through the Research Pharmacy if needed for subject safety, but otherwise the blind will be maintained until study completion and database lock.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Model Details: This study employs a parallel-group design where hospitalized patients with decompensated cirrhosis and acute kidney injury are randomized in a 2:1 ratio to receive either droxidopa or matching placebo. Both groups will receive the intervention concurrently over the 28-day treatment period, with identical titration protocols and assessment schedules. Participants in the active arm will receive droxidopa initially at 100 mg three times daily, titrated based on mean arterial pressure response, while the control arm will receive identical-appearing placebo capsules following the same schedule and titration protocol to maintain blinding.

Study Record Dates

• First Submitted: April 15, 2025
• First Posted: April 22, 2025
• Study Start: May 27, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: June 4, 2025

Record last verified: 2025-06

Locations

US (1)