Portal Vein ThrombosisPhase 1PiVoTNCT04055389
Preventing de Novo Portal Vein Thrombosis With Antithrombin-III in Patients With Cirrhosis
A Phase 1 study testing Antithrombin III in people with Portal Vein Thrombosis and Cirrhosis, Liver, run by Jonathan Stine at 1 site in United States.
Trial summary
To prevent portal vein thrombosis (PVT) in patients with cirrhosis at risk for PVT by pharmacologic prophylaxis with intravenous antithrombin (AT-III). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Portal Vein Thrombosis, Cirrhosis, Liver
- What is being tested?
- Antithrombin III
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jan 2021to 22 Feb 2022
- Phase
- Phase 1
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Cirrhosis documented by:
- Liver biopsy OR
- Clinical, imaging, and laboratory findings consistent with cirrhosis AND
- Disease process etiologic for cirrhosis (e.g., chronic viral hepatitis, non-alcoholic steatohepatitis, history of alcohol abuse, cholestatic liver disease)
- Flow in main portal vein less than 15 cm/sec or reversal of flow as assessed by Doppler ultrasonography
- Age greater than or equal to 18 and less than or equal to 75 years
Show all 40Show fewer
- AT-III <70%
- Platelet count greater than or equal to 55,000 per uL
- Laboratories reflective of general health status (normal):
- White blood cell count (4-10.4 K/uL)
- Hemoglobin (11.7-15.0 g/dL) and hematocrit (35-44%)
- Creatinine (0.60-1.00 mg/dL) • Child Pugh Turcotte (CPT) Class A cirrhosis
- 3.2 Exclusion Criteria
- Allergy to AT-III or one of its ingredients
- CPT Class B or C cirrhosis
- Coagulopathy as indicated by International Normalized Ratio (INR) >= 2.2 or an inherited coagulation disorder
- Active hepatitis C infection expecting to initiate HCV therapy within the next two years
- Established PVT or cavernoma
- Transvenous portosystemic shunt (TIPS) placement
- Previous liver transplantation
- Increased risk of bleeding:
- Active pathological bleeding including subjects with actively bleeding esophageal varices
- History of intracranial bleeding
- Unexplained gastrointestinal bleeding
- Subjects with large esophageal varices, or varices with endoscopic stigmata of bleeding (e.g., red wale sign)
- Subjects with gastric or intestinal varices
- Subjects who are taking medicines that increase the risk of thrombosis (e.g. tamoxifen)
- Subjects with any clinically significant bleeding within the last one month
- Need for therapeutic anticoagulation for another indication
- Concurrent use of antiplatelet medications excluding aspirin 81 mg once daily as aspirin at this dosage does not increase bleeding when given concomitantly with AT-III
- Pregnancy or breastfeeding
- Recent major surgery within six weeks
- Inability or unwilling to give informed consent
- Hepatocellular carcinoma [diagnosed by cross-sectional imaging, e.g., computed tomography (CT) or magnetic resonance imaging (MRI)] or another active malignancy
- Predicted lifespan less than two years
- Severe concurrent disease threatening successful completion of the trial in the opinion of the study principle investigator
- Ongoing substance abuse as judged by the study principal investigator and confirmed by an eight-panel urine drug test at screening
- Significant alcohol consumption (20g/day for women and 30g/day for men)
- Human Immunodeficiency Virus infection
- Worsening liver function based on the two initial laboratory values used to establish baseline laboratory measurements (section 7.2.2 Monitoring and Intervention Plan for Drug-induced Liver Injury)
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Penn State College of Medicine
Hershey, Pennsylvania, 17033
About this study
Official title: Preventing de Novo Portal Vein Thrombosis With Antithrombin-III in Patients With Cirrhosis: A Randomized, Double-blinded, Placebo - Controlled Trial (PiVoT-AC Trial)
To prevent portal vein thrombosis (PVT) in patients with cirrhosis at risk for PVT by pharmacologic prophylaxis with intravenous antithrombin (AT-III).
Read the detailed description
PVT is a common complication in patients with cirrhosis, affecting 10% to 25% of patients. PVT is a potentially life-threatening occurrence, complicating transplant candidacy and reducing five-year survival. In addition to the mortality risk posed by PVT, microthrombi within the liver have been linked to decompensation due to the phenomenon of parenchymal extinction. Because of the developing understanding of a baseline hypercoagulable state in many cirrhosis patients, recent studies have demonstrated the benefit of prophylactic anticoagulation with enoxaparin in patients with cirrhosis to prevent PVT. In addition to the benefit in reducing PVT, prophylactic anticoagulation was also found to reduce liver decompensation and improve overall survival.
Risk factors for PVT are well described. The strongest independent risk factor for PVT is portal vein velocity. For each 1 cm/s decrease in portal vein velocity, PVT risk increases 16%. Portal vein velocity <15cm/sec is the best-established cutoff for predicting the development of de novo PVT over the ensuing twelve months.
In addition, patients with cirrhosis and venous thromboembolism (PVT, deep vein thrombosis, pulmonary embolus) have abnormally low levels of AT-III. A recent report by the NPB-06 study group suggest that administering intravenous AT-III at dosage of 1500 units/day for five consecutive days in patients with cirrhosis and AT-III <70% serum level is a safe and effective treatment for PVT with promising short-term partial and complete resolution of PVT. Despite this, the role of AT repletion in preventing PVT remains unknown.
- Conditions
- Portal Vein Thrombosis, Cirrhosis, Liver
- Being tested
- Antithrombin III, Placebo
- Medical subject headings
- Liver Cirrhosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Antithrombin IIIDrug
Patients with reversal of flow or sluggish flow in the main portal vein (<15 cm/s by Doppler ultrasound exam) will be enrolled and randomized to either weekly infusions of AT-III (half-life ~4 days) at a weight-based dosage according to the following formula:
[Desired level of AT (100%) - Subject level of AT (%)] * subject weight (kg) 1.4
or placebo for 24 weeks of therapy.
PlaceboOther
No study drug
| Study group | Role | What they receive |
|---|---|---|
| AT-III treatment | Experimental | Not described Receives: Drug: Antithrombin III |
| Placebo | Placebo comparator | Not described Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Development of PVT
incident of PVT measured by ultrasound at different time points
Measured: up to 72 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2019
- Study start1 Jan 2021
- Primary completion22 Feb 2022
- Study completion22 Feb 2022
Why it stopped: Challenges with recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Portal Vein ThrombosisStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jonathan Stine
- Sponsor type
- University, hospital or other
- Collaborators
- Grifols Therapeutics LLC
- Responsible party
- Sponsor-investigator, Jonathan Stine, Milton S. Hershey Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04055389
- Sponsor's protocol ID
- STUDY00013058
- Acronym
- PiVoT
- Status last verified
- Feb 2022
- First submitted
- 7 Aug 2019
- Last updated
- 10 Mar 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Preventing de Novo Portal Vein Thrombosis With Antithrombin-III in Patients With Cirrhosis: A Randomized, Double-blinded, Placebo - Controlled Trial (PiVoT-AC Trial)
- ClinicalTrials.gov ID
- NCT04055389
- Acronym / sponsor ID
- PiVoT / STUDY00013058
- Conditions
- Portal Vein Thrombosis, Cirrhosis, Liver
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Challenges with recruitment
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Jonathan StineUniversity, hospital or other
- Collaborators
- Grifols Therapeutics LLC
- Study start
- 1 Jan 2021 (actual)
- Primary completion
- 22 Feb 2022 (actual)
- Study completion
- 22 Feb 2022 (actual)
- First posted
- 13 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.
To prevent portal vein thrombosis (PVT) in patients with cirrhosis at risk for PVT by pharmacologic prophylaxis with intravenous antithrombin (AT-III).
Detailed description
PVT is a common complication in patients with cirrhosis, affecting 10% to 25% of patients. PVT is a potentially life-threatening occurrence, complicating transplant candidacy and reducing five-year survival. In addition to the mortality risk posed by PVT, microthrombi within the liver have been linked to decompensation due to the phenomenon of parenchymal extinction. Because of the developing understanding of a baseline hypercoagulable state in many cirrhosis patients, recent studies have demonstrated the benefit of prophylactic anticoagulation with enoxaparin in patients with cirrhosis to prevent PVT. In addition to the benefit in reducing PVT, prophylactic anticoagulation was also found to reduce liver decompensation and improve overall survival.
Risk factors for PVT are well described. The strongest independent risk factor for PVT is portal vein velocity. For each 1 cm/s decrease in portal vein velocity, PVT risk increases 16%. Portal vein velocity <15cm/sec is the best-established cutoff for predicting the development of de novo PVT over the ensuing twelve months.
In addition, patients with cirrhosis and venous thromboembolism (PVT, deep vein thrombosis, pulmonary embolus) have abnormally low levels of AT-III. A recent report by the NPB-06 study group suggest that administering intravenous AT-III at dosage of 1500 units/day for five consecutive days in patients with cirrhosis and AT-III <70% serum level is a safe and effective treatment for PVT with promising short-term partial and complete resolution of PVT. Despite this, the role of AT repletion in preventing PVT remains unknown.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AT-III treatment | Experimental | Drug: Antithrombin III |
| Placebo | Placebo comparator | Other: Placebo |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (40 listed)
- Liver biopsy OR
- Clinical, imaging, and laboratory findings consistent with cirrhosis AND
- Disease process etiologic for cirrhosis (e.g., chronic viral hepatitis, non-alcoholic steatohepatitis, history of alcohol abuse, cholestatic liver disease)
- White blood cell count (4-10.4 K/uL)
- Hemoglobin (11.7-15.0 g/dL) and hematocrit (35-44%)
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| Antithrombin IIIPatients with reversal of flow or sluggish flow in the main portal vein (<15 cm/s by Doppler ultrasound exam) will be enrolled and randomized to either weekly infusions of AT-III (half-life ~4 days) at a weight-based dosage according to the following formula: [Desired level of AT (100%) - Subject level of AT (%)] * subject weight (kg) 1.4 or placebo for 24 weeks of therapy. | Drug | AT-III treatment |
| PlaceboNo study drug | Other | Placebo |
Primary outcome
Development of PVT
Time frame: up to 72 weeks
incident of PVT measured by ultrasound at different time points
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 10 Mar 2022.
- 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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Antithrombin III in people with Portal Vein Thrombosis and Cirrhosis, Liver, run by Jonathan Stine at 1 site in United States.
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 40 inclusion and 0 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 10 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Development of PVT (time frame: up to 72 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Mar 2022.