Droxidopa for Liver Cirrhosis and Acute Kidney Injury

(DROP-AKI Trial)

Overseen By Giuseppe Cullaro, MD, MAS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Giuseppe Cullaro, MD

Must not be taking: MAOIs, Norepinephrine reuptake inhibitors

Disqualifiers: Severe cardiovascular disease, Age >70, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 28 days

75 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether droxidopa, a medication that can raise blood pressure, can improve kidney function in people with liver cirrhosis who develop kidney problems while hospitalized. Droxidopa may safely increase blood pressure, aiding kidney recovery without intensive treatments. Participants will take either droxidopa or a placebo for 28 days, with monitoring for changes in blood pressure and kidney health. Suitable candidates have liver cirrhosis, are hospitalized at Columbia University Irving Medical Center, and have developed kidney injury there. As a Phase 2 trial, this research measures droxidopa's effectiveness in an initial, smaller group, allowing participants to contribute to significant medical advancements.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications that could interact with droxidopa, such as MAOI inhibitors, norepinephrine reuptake inhibitors, and other investigational drugs.

Is there any evidence suggesting that droxidopa is likely to be safe for humans?

Previous studies have used droxidopa to increase blood pressure in individuals with conditions like neurogenic orthostatic hypotension, where blood pressure drops significantly upon standing. Research has shown that the treatment is generally well-tolerated. Some patients reported mild to moderate side effects, such as headaches or dizziness, which often decrease as the body adjusts to the medication.

The FDA has already approved droxidopa for treating low blood pressure in certain conditions, indicating a recognized safety profile. However, its use in individuals with liver cirrhosis and acute kidney injury remains under study, suggesting potential unknown risks for these patients.

Overall, current evidence suggests droxidopa is reasonably safe, but evaluating risks requires considering the specific health conditions of participants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for liver cirrhosis and acute kidney injury, which often focus on managing symptoms or delaying disease progression, droxidopa offers a unique approach by potentially improving blood flow through its role as a norepinephrine precursor. This means it could enhance blood pressure regulation, which is critical for patients with these conditions. Researchers are excited because droxidopa might provide a new way to address underlying issues rather than just treating symptoms, offering hope for more effective management of these challenging conditions.

What evidence suggests that droxidopa might be an effective treatment for kidney injury in liver cirrhosis?

Research has shown that droxidopa, an oral medication, can improve blood flow to the kidneys in individuals with liver cirrhosis who have kidney problems. In this trial, participants in the experimental arm will receive droxidopa, which raises blood pressure and may enhance kidney function and support recovery. It aids the body in producing chemicals that increase blood pressure and improve circulation. Early studies suggest it might effectively treat hepatorenal syndrome, a type of kidney failure in people with severe liver disease, especially when other treatments have failed. While more research is needed, these early results offer promise for those seeking new treatment options. ^{1 2 3 4 6}

Who Is on the Research Team?

Giuseppe Cullaro, MD, MAS

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

This trial is for hospitalized patients with liver cirrhosis who have developed acute kidney injury. Participants should not be in intensive care or require invasive treatments and must be able to take oral medication.

Inclusion Criteria

Ability to provide informed consent by subject or legally authorized representative

Consent to blood and urine collection for biomarker analysis

For women of childbearing potential: negative pregnancy test and agreement to use effective contraception

Exclusion Criteria

Any episode of a SBP ≥ 180 mmHg or a DBP ≥ 120 mmHg on two measurements, 1 minute apart

My kidney function is severely impaired.

Pregnancy or breastfeeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either droxidopa or placebo for 28 days to assess changes in mean arterial pressure and kidney function

28 days

Daily monitoring during hospitalization

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

What Are the Treatments Tested in This Trial?

Interventions

• Droxidopa

Trial Overview The study tests if droxidopa, an oral medication, can improve blood pressure and aid kidney recovery in cirrhotic patients with kidney injury. It compares droxidopa's effectiveness against a placebo over a period of 28 days, followed by monitoring for another 30 days.

How Is the Trial Designed?

Group I: Droxidopa Experimental Treatment 1 Intervention

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.

Group II: Placebo Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

Giuseppe Cullaro, MD

Lead Sponsor

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06937307

NCT06937307 | Droxidopa to Increase Mean Arterial ... 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 ...

2. trialx.com trialx.com/clinical-trials/listings/298209/droxidopa-to-increase-mean-arterial-pressure-in-decompensated-cirrhosis-patients-with-acute-kidney-injury/

Decompensated Cirrhosis of Liver | Acute Kidney Injury ) ( ... Overview. This study tests whether a medication called droxidopa can help improve blood flow to the kidneys in people with liver cirrhosis ...

3. withpower.com withpower.com/trial/phase-2-liver-cirrhosis-4-2025-821b0

Droxidopa for Liver Cirrhosis and Acute Kidney Injury 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 ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35426352/

Droxidopa in the Management of Hepatorenal Syndrome We report the use of droxidopa, an oral norepinephrine precursor, to aid in the management of HRS-AKI refractory to first-line therapy. Summary: ...

5. trial.medpath.com trial.medpath.com/clinical-trial/29f493854bb1aca6/nct06937307-droxidopa-arterial-pressure-cirrhosis-kidney-injury

Droxidopa to Increase Mean Arterial Pressure in ... - MedPath This study tests whether a medication called droxidopa can help improve blood flow to the kidneys in people with liver cirrhosis who develop ...

6. jacc.org jacc.org/doi/10.1016/j.jacc.2020.06.070

Contemporary Management of Severe Acute Kidney Injury ... Patients who require acute RRT have a significant risk of mortality and long-term dialysis dependence, emphasizing the importance of appropriate patient ...