Hepatorenal SyndromePhase 2ANTHEMNCT04048707
Angiotensin 2 for Hepatorenal Syndrome
A Phase 2 study testing Angiotensin II, Midodrine and Octreotide in people with Hepatorenal Syndrome and Cirrhosis, run by University of California, Los Angeles.
Trial summary
Hepatorenal syndrome (HRS) is a disease in which patients with cirrhosis (end stage liver failure) develop secondary kidney injury and failure. The current treatment available in the United States is a combination of octreotide and midodrine, which are meant to decrease the release of those hormones and raise the… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatorenal Syndrome, Cirrhosis, Kidney Failure, Acute
- What is being tested?
- Angiotensin II, Midodrine and Octreotide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 Jul 2021to 1 Jul 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Age <18 years
- Current or anticipated (within 24 hours) need for renal replacement therapy (RRT)
- Cr > 6 mg/dl
- Renal transplantation status
- Fractional Excretion of Sodium (FeNa) > 2%
- Pregnancy
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- Recent Cerebrovascular Accident (CVA), Myocardial Infarction (MI), venous or arterial thrombosis (within last 3 months)
- Known hypercoagulable state other than cirrhosis
- Uncontrolled hypertension (SBP > 160)
- Anticipated mortality within 72 hours
- Inability to obtain consent.
About this study
Official title: Angiotensin 2 as a Novel Treatment for Hepatorenal Syndrome
Hepatorenal syndrome (HRS) is a disease in which patients with cirrhosis (end stage liver failure) develop secondary kidney injury and failure. The current treatment available in the United States is a combination of octreotide and midodrine, which are meant to decrease the release of those hormones and raise the blood pressure, respectively, which would increase blood flow to the kidneys. Angiotensin 2 (Ang2) is a new vasopressor drug that was approved by the FDA in December 2017 for patients with low blood pressure and has been shown to have similar effects to octreotide and midodrine.
This study will investigate whether Ang2 reverses HRS among patients admitted to the intensive care unit (ICU) at Ronald Reagan Medical Center. Our study population will be patients with HRS who are already or will be admitted to the ICU. HRS will be defined by new internationally accepted guidelines published by the International Club of Ascites. All patients who are consented will undergo an Ang2 response trial, where low-dose Ang2 will be administered for 4 hours to see how the patients respond. This will help us characterize the nature of the patients' kidney failure for later analysis. Patients will then be randomized into the control group or the study group. Patients in the control group will receive octreotide (a subcutaneous injection) and midodrine (an oral drug). Patients in the study group will continue receiving intravenous infusion of Ang2. Patients in both groups will also receive albumin, a protein found commonly in human blood. Treatment will continue in both groups for four days, until complete reversal of HRS, dialysis, or death.
Our primary outcome will be rate of reversal of HRS, defined as improvement in kidney function.
- Conditions
- Hepatorenal Syndrome, Cirrhosis, Kidney Failure, Acute
- Being tested
- Angiotensin II, Midodrine, Octreotide, Albumin solution
- Medical subject headings
- Hepatorenal Syndrome, Fibrosis, Acute Kidney Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Angiotensin IIDrug
Also called Giapreza
Intravenous
MidodrineDrug
Pill
OctreotideDrug
Subcutaneous
Albumin solutionDrug
Intravenous suspension
| Study group | Role | What they receive |
|---|---|---|
| Midodrine/Octreotide | Active comparator | This arm will receive standard of care treatment of midodrine, octreotide, and albumin. Receives: Drug: Midodrine; Drug: Octreotide; Drug: Albumin solution |
| Angiotensin 2 | Experimental | This arm will receive the experimental treatment of angiotensin 2 infusion and albumin. Receives: Drug: Angiotensin II; Drug: Albumin solution |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reversal of hepatorenal syndrome
Partial or complete reversal of HRS. Serum creatinine will be measured daily and compared against the patient's baseline creatinine.
Partial reversal is defined defined as improvement of at least one AKI stage as defined by International Club of Ascites Acute Kidney Injury (ICA-AKI) criteria Complete defined as improvement of serum creatinine to within 0.3 mg/dl of baseline value).
ICA-AKI criteria:
- Stage 1: increase in sCr ≥0.3 mg/dl (26.5 μmol/L) or an increase in sCr ≥1.5-fold to 2-fold from baseline
- Stage 2: increase in sCr >2-fold to 3-fold from baseline
- Stage 3: increase of sCr >3-fold from baseline or sCr ≥4.0 mg/dl (353.6 μmol/L) with an acute increase ≥0.3 mg/dl (26.5 μmol/L) or initiation of renal replacement therapy Angeli P et al. J Hepatology 2015:62(968-974)
Measured: 4 days
Secondary outcomes (4)
Need for renal replacement therapy
The treating team with the assistance of nephrology will assess the acute need for dialysis on a daily basis. If the patient does require urgent hemodialysis at their determination, this will be noted. The proportion of each group who required hemodialysis will be compared.
Measured: 4 days
Mortality
In-hospital mortality
Measured: 28 days
Serum sodium
Change in serum sodium from the beginning of the study to the end of the study.
Measured: 4 days
Relapse of hepatorenal syndrome
Recurrence of HRS-AKI after withdrawal of study drug, defined as a worsening of AKI by at least one stage according to ICA-AKI criteria AKI grade as defined by ICA-AKI criteria (J Hepatology 2015:62[968-974])
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2019
- Study start1 Jul 2021 (estimated)
- Primary completion30 Jun 2023 (estimated)
- Study completion1 Jul 2023 (estimated)
Why it stopped: Funding issues; the study was never started
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hepatorenal SyndromeStudies of the same condition, open and under way.
- More trials run by University of California, Los AngelesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04048707
- Sponsor's protocol ID
- #19-005718
- Acronym
- ANTHEM
- Status last verified
- Mar 2024
- First submitted
- 29 Jul 2019
- Last updated
- 6 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Tumlin JA, Murugan R, Deane AM, Ostermann M, Busse LW, Ham KR, Kashani K, Szerlip HM, Prowle JR, Bihorac A, Finkel KW, Zarbock A, Forni LG, Lynch SJ, Jensen J, Kroll S, Chawla LS, Tidmarsh GF, Bellomo R; Angiotensin II for the Treatment of High-Output Shock 3 (ATHOS-3) Investigators. Outcomes in Patients with Vasodilatory Shock and Renal Replacement Therapy Treated with Intravenous Angiotensin II. Crit Care Med. 2018 Jun;46(6):949-957. doi: 10.1097/CCM.0000000000003092.
PubMed 29509568Khanna A, Ostermann M, Bellomo R. Angiotensin II for the Treatment of Vasodilatory Shock. N Engl J Med. 2017 Dec 28;377(26):2604. doi: 10.1056/NEJMc1714511. No abstract available.
PubMed 29281568
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Angiotensin 2 as a Novel Treatment for Hepatorenal Syndrome
- ClinicalTrials.gov ID
- NCT04048707
- Acronym / sponsor ID
- ANTHEM / #19-005718
- Conditions
- Hepatorenal Syndrome, Cirrhosis, Kidney Failure, Acute
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Funding issues; the study was never started
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Study start
- 1 Jul 2021 (estimated)
- Primary completion
- 30 Jun 2023 (estimated)
- Study completion
- 1 Jul 2023 (estimated)
- First posted
- 7 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Hepatorenal syndrome (HRS) is a disease in which patients with cirrhosis (end stage liver failure) develop secondary kidney injury and failure. The current treatment available in the United States is a combination of octreotide and midodrine, which are meant to decrease the release of those hormones and raise the blood pressure, respectively, which would increase blood flow to the kidneys. Angiotensin 2 (Ang2) is a new vasopressor drug that was approved by the FDA in December 2017 for patients with low blood pressure and has been shown to have similar effects to octreotide and midodrine.
This study will investigate whether Ang2 reverses HRS among patients admitted to the intensive care unit (ICU) at Ronald Reagan Medical Center. Our study population will be patients with HRS who are already or will be admitted to the ICU. HRS will be defined by new internationally accepted guidelines published by the International Club of Ascites. All patients who are consented will undergo an Ang2 response trial, where low-dose Ang2 will be administered for 4 hours to see how the patients respond. This will help us characterize the nature of the patients' kidney failure for later analysis. Patients will then be randomized into the control group or the study group. Patients in the control group will receive octreotide (a subcutaneous injection) and midodrine (an oral drug). Patients in the study group will continue receiving intravenous infusion of Ang2. Patients in both groups will also receive albumin, a protein found commonly in human blood. Treatment will continue in both groups for four days, until complete reversal of HRS, dialysis, or death.
Our primary outcome will be rate of reversal of HRS, defined as improvement in kidney function.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Midodrine/Octreotide | Active comparator | Drug: Midodrine, Drug: Octreotide, Drug: Albumin solutionThis arm will receive standard of care treatment of midodrine, octreotide, and albumin. |
| Angiotensin 2 | Experimental | Drug: Angiotensin II, Drug: Albumin solutionThis arm will receive the experimental treatment of angiotensin 2 infusion and albumin. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (11 listed)
- Age <18 years
- Current or anticipated (within 24 hours) need for renal replacement therapy (RRT)
- Cr > 6 mg/dl
- Renal transplantation status
- Fractional Excretion of Sodium (FeNa) > 2%
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Angiotensin IIAlso: GiaprezaIntravenous | Drug | Angiotensin 2 |
| MidodrinePill | Drug | Midodrine/Octreotide |
| OctreotideSubcutaneous | Drug | Midodrine/Octreotide |
| Albumin solutionIntravenous suspension | Drug | Angiotensin 2, Midodrine/Octreotide |
Primary outcome
Reversal of hepatorenal syndrome
Time frame: 4 days
Partial or complete reversal of HRS. Serum creatinine will be measured daily and compared against the patient's baseline creatinine. Partial reversal is defined defined as improvement of at least one AKI stage as defined by International Club of Ascites Acute Kidney Injury (ICA-AKI) criteria Complete defined as improvement of serum creatinine to within 0.3 mg/dl of baseline value). ICA-AKI criteria: * Stage 1: increase in sCr ≥0.3 mg/dl (26.5 μmol/L) or an increase in sCr ≥1.5-fold to 2-fold from baseline * Stage 2: increase in sCr >2-fold to 3-fold from baseline * Stage 3: increase of sCr >3-fold from baseline or sCr ≥4.0 mg/dl (353.6 μmol/L) with an acute increase ≥0.3 mg/dl (26.5 μmol/L) or initiation of renal replacement therapy Angeli P et al. J Hepatology 2015:62(968-974)
4 secondary outcomes
Need for renal replacement therapy
Time frame: 4 days
Mortality
Time frame: 28 days
Serum sodium
Time frame: 4 days
Relapse of hepatorenal syndrome
Time frame: 14 days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2024.
- Background: PubMed 29509568Tumlin JA, Murugan R, Deane AM, Ostermann M, Busse LW, Ham KR, Kashani K, Szerlip HM, Prowle JR, Bihorac A, Finkel KW, Zarbock A, Forni LG, Lynch SJ, Jensen J, Kroll S, Chawla LS, Tidmarsh GF, Bellomo R; Angiotensin II for the Treatment of High-Output Shock 3 (ATHOS-3) Investigators. Outcomes in Patients with Vasodilatory Shock and Renal Replacement Therapy Treated with Intravenous Angiotensin II. Crit Care Med. 2018 Jun;46(6):949-957. doi: 10.1097/CCM.0000000000003092.
- Background: PubMed 29281568Khanna A, Ostermann M, Bellomo R. Angiotensin II for the Treatment of Vasodilatory Shock. N Engl J Med. 2017 Dec 28;377(26):2604. doi: 10.1056/NEJMc1714511. No abstract available.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Angiotensin II, Midodrine and Octreotide in people with Hepatorenal Syndrome and Cirrhosis, run by University of California, Los Angeles.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 6 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Reversal of hepatorenal syndrome (time frame: 4 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04048707, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2024.