Heparin-induced ThrombocytopeniaPhase 2NCT03594045
Efficacy and Safety of Apixaban in the Treatment of Heparin Induced Thrombocytopenia (HIT)
A Phase 2 study testing Apixaban in people with Heparin-induced Thrombocytopenia and Heparin-induced Thrombocytopenia and Thrombosis, run by Massachusetts General Hospital at 3 sites in United States.
Trial summary
This research study is studying a drug as a possible treatment for heparin induced thrombocytopenia (HIT) or Heparin-induced Thrombocytopenia and Thrombosis (HITT). The drug involved in this study is apixaban. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heparin-induced Thrombocytopenia, Heparin-induced Thrombocytopenia and Thrombosis
- What is being tested?
- Apixaban
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 3 sitesUnited States
- Study dates
- 18 Dec 2018to 30 Oct 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Hospitalized patients at MGH and participating Dana Farber/Harvard Cancer Center (DF/HCC) sites.
- Patient must have a diagnosis of HIT or high clinical suspicion of HIT, with a 4 T score of ≥ 5 as calculated by the following criteria:
- Thrombocytopenia
- Platelet count fall >50 percent and nadir ≥20,000/microL - 2 points
- Platelet count fall 30 to 50 percent or nadir 10 to 19,000/microL - 1 points
- Platelet count fall <30 percent or nadir <10,000/microL - 0 points
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- Timing of platelet count fall
- Clear onset between days 5 and 10 or platelet count fall at ≤1 day if prior heparin exposure within the last 30 days - 2 points
- Consistent with fall at 5 to 10 days but unclear (eg, missing platelet counts), onset after day 10, or fall ≤1 day with prior heparin exposure within 30 to 100 days - 1 point
- Platelet count fall at <4 days without recent exposure - 0 points
- Thrombosis or other sequelae
- Confirmed new thrombosis, skin necrosis, or acute systemic reaction after intravenous unfractionated heparin bolus - 2 points
- Progressive or recurrent thrombosis, non-necrotizing (erythematous) skin lesions, or suspected thrombosis that has not been proven - 1 point
- None - 0 points
- Other causes for thrombocytopenia
- None apparent - 2 points
- Possible - 1 point
- Definite - 0 points
- Prior to or immediately subsequent to enrollment, the patient must have the diagnosis confirmed by Heparin-PF4 EIA or other accepted confirmatory test to remain on study.
- Patients can be treated with argatroban, bivalirudin or fondaparinux for up to 72 hours prior to enrollment.
- Age 18 years or older.
- ECOG performance status ≤2 (Karnofsky ≥60%)
- Participants must have organ and marrow function as defined below:
- absolute neutrophil count ≥1,500/mcL
- AST(SGOT) and ALT(SGPT) ≤2.5 × institutional upper limit of normal
- creatinine clearance ≥25 mL/min as was used in the AMPLIFY trial16
- The effects of apixaban on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study entry, for the duration of the study participation, and 4 months after completion of apixaban administration.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Patient requires anticoagulation for a mechanical heart valve.
- Patient requires:
- anticoagulation for another indication for long-term anticoagulation therapy,
- dual antiplatelet therapy,
- treatment with aspirin at a dose of more than 162 mg daily
- Patient has signs of active or ongoing clinically significant hemorrhage.
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- Patient has hereditary or acquired coagulopathy or bleeding disorder.
- Patient has a contraindication to apixaban.
- Participants receiving any medications or substances that are inhibitors or inducers of cytochrome P-450 3A4 or p-glycoprotein are ineligible. Because this list of these agents are constantly changing, it is important to regularly consult a frequently-updated list. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product.
- Patient has severe renal insufficiency (CrCl <25 ml/min-as used in the AMPLIFY trial)
- Patient has hepatic disease (including Child-Pugh B and C) associated with coagulopathy or clinically relevant bleeding risk.
- Recent (previous seven days), or complicated lumbar puncture or epidural catheter placement or removal.
- Patient has high potential need to undergo a surgical or major invasive procedure in the near future.
- Patient has a history of uncorrected cerebral aneurysm, intracranial tumor or hemorrhagic cerebrovascular accident.
- Patient refuses to receive transfused blood products should this intervention become clinically indicated.
- Patient is taking or has been taking an investigational drug within the previous 30 days prior to enrollment.
- In the judgment of the investigator, any disease or circumstance that would interfere with the objectives of the study.
- Participants with known brain metastases.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to apixaban.
- Uncontrolled intercurrent illness.
- Pregnant women are excluded; breastfeeding should be discontinued if the mother is treated with apixaban.
- Prior treatment with a non-heparin anticoagulant while awaiting study enrollment is not an exclusion.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Massachusetts General Hospital
Boston, Massachusetts, 02214
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Brigham and Women Hospital
Boston, Massachusetts, 02215
About this study
Official title: A Phase II Study to Evaluate the Efficacy and Safety of Apixaban in the Treatment of Heparin Induced Thrombocytopenia (HIT)
This research study is studying a drug as a possible treatment for heparin induced thrombocytopenia (HIT) or Heparin-induced Thrombocytopenia and Thrombosis (HITT).
The drug involved in this study is apixaban.
Read the detailed description
This research study is a Phase II clinical trial.
The FDA (the U.S. Food and Drug Administration) has not approved apixaban as a treatment option for this specific disease but it has been approved for other uses.
HIT and HITT are common and severe complications of heparin therapy. Once patients are diagnosed with either one of these, they are typically switched to a non-heparin anticoagulant (a type of drug that thins your blood). As of now the only drug that is FDA approved for HIT or HITT is argatroban, which is administered continuously through an IV over multiple days and is extremely costly.
In this research study, the investigators are researching the activity and tolerability of apixaban in participants with HIT or HITT. The investigators believe that apixaban will work just as well as argatroban and will be more convenient for this population. The oral route of apixaban allows for the potential outpatient treatment of HIT or HITT which is both convenient and less expensive than treatment with argatroban.
- Being tested
- Apixaban
- Keywords
- Heparin-induced Thrombocytopenia
- Medical subject headings
- Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ApixabanDrug
Apixaban is an anticoagulant that works by inhibiting the coagulation factor, Factor Xa.
| Study group | Role | What they receive |
|---|---|---|
| Apixaban for HIT | Experimental | Patients with Heparin Induced Thrombocytopenia (HIT) will receive Apixaban, at an initial dose of 10 mg orally twice a day for 7 days followed by 5 mg twice a day for a total of 30 days. Receives: Drug: Apixaban |
| Apixaban for HITT | Experimental | Patients with Heparin Induced Thrombocytopenia with Thrombosis (HITT) will receive Apixaban, at an initial dose of 10 mg orally twice a day for 7 days followed by 5 mg twice a day for a total of 3 months. Receives: Drug: Apixaban |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cumulative Incidence of New Symptomatic Thromboembolic Complications (TEC) Within 30 Days of the Initiation of Apixaban
New TEC
Measured: 30 days
Secondary outcomes (7)
Composite Cumulative Incidence of All-cause Mortality, Limb Amputation and New TEC
Composite cumulative incidence
Measured: From the start of treatment until 30 days after the end of treatment, up to 60 days total for participants with HIT and up to 120 days total for participants with HITT
Composite Cumulative Incidence of New TEC and Major Bleeding
Composite cumulative incidence
Measured: From the start of treatment until 30 days after the end of treatment, up to 60 days total for participants with HIT and up to 120 days total for participants with HITT
Cumulative Incidence of Major Bleeding
Major Bleeding
Measured: From the start of treatment until 30 days after the end of treatment, up to 60 days total for participants with HIT and up to 120 days total for participants with HITT
Time to Platelet Recovery
The time to platelet recovery serves as a surrogate index of the activity of apixaban.
Measured: From the start of treatment until time of platelet recovery, up to 60 days total for participants with HIT and up to 120 days total for participants with HITT
Cumulative Incidence of All Cause Mortality
Death due to any cause during treatment or the follow-up period following treatment.
Measured: From the start of treatment until the time of death or until 30 days after the end of treatment, up to 60 days total for participants with HIT and up to 120 days total for participants with HITT
Cumulative Incidence of Limb Amputation
Measured: From the start of treatment until 30 days after the end of treatment, up to 60 days total for participants with HIT and up to 120 days total for participants with HITT
Cumulative Incidence of New Thromboembolic Complications (TEC)
New TEC during the study.
Measured: From the start of treatment until 30 days after the end of treatment, up to 60 days total for participants with HIT and up to 120 days total for participants with HITT
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2018
- Study start18 Dec 2018
- Primary completion30 Oct 2019
- Study completion30 Oct 2019
Why it stopped: Withdrawal of funding by sponsor
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Heparin-induced ThrombocytopeniaStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Principal investigator, Rachel P. Rosovsky, MD, Massachusetts General Hospital
- Investigators
- Rachel P Rosovsky, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03594045
- Sponsor's protocol ID
- 18-153
- Status last verified
- Nov 2020
- First submitted
- 10 Jul 2018
- Last updated
- 23 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- 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 23 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study to Evaluate the Efficacy and Safety of Apixaban in the Treatment of Heparin Induced Thrombocytopenia (HIT)
- ClinicalTrials.gov ID
- NCT03594045
- Acronym / sponsor ID
- 18-153
- Keywords
- Heparin-induced Thrombocytopenia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Withdrawal of funding by sponsor
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 18 Dec 2018 (actual)
- Primary completion
- 30 Oct 2019 (actual)
- Study completion
- 30 Oct 2019 (actual)
- First posted
- 20 Jul 2018 (actual)
- Results
- Posted 23 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research study is studying a drug as a possible treatment for heparin induced thrombocytopenia (HIT) or Heparin-induced Thrombocytopenia and Thrombosis (HITT).
The drug involved in this study is apixaban.
Detailed description
This research study is a Phase II clinical trial.
The FDA (the U.S. Food and Drug Administration) has not approved apixaban as a treatment option for this specific disease but it has been approved for other uses.
HIT and HITT are common and severe complications of heparin therapy. Once patients are diagnosed with either one of these, they are typically switched to a non-heparin anticoagulant (a type of drug that thins your blood). As of now the only drug that is FDA approved for HIT or HITT is argatroban, which is administered continuously through an IV over multiple days and is extremely costly.
In this research study, the investigators are researching the activity and tolerability of apixaban in participants with HIT or HITT. The investigators believe that apixaban will work just as well as argatroban and will be more convenient for this population. The oral route of apixaban allows for the potential outpatient treatment of HIT or HITT which is both convenient and less expensive than treatment with argatroban.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Apixaban for HIT | Experimental | Drug: ApixabanPatients with Heparin Induced Thrombocytopenia (HIT) will receive Apixaban, at an initial dose of 10 mg orally twice a day for 7 days followed by 5 mg twice a day for a total of 30 days. |
| Apixaban for HITT | Experimental | Drug: ApixabanPatients with Heparin Induced Thrombocytopenia with Thrombosis (HITT) will receive Apixaban, at an initial dose of 10 mg orally twice a day for 7 days followed by 5 mg twice a day for a total of 3 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- Hospitalized patients at MGH and participating Dana Farber/Harvard Cancer Center (DF/HCC) sites.
- Patient must have a diagnosis of HIT or high clinical suspicion of HIT, with a 4 T score of ≥ 5 as calculated by the following criteria:
- Thrombocytopenia
- Timing of platelet count fall
- Thrombosis or other sequelae
Key exclusion criteria (22 listed)
- Patient requires anticoagulation for a mechanical heart valve.
- Patient requires:
- Patient has signs of active or ongoing clinically significant hemorrhage.
- Patient has hereditary or acquired coagulopathy or bleeding disorder.
- Patient has a contraindication to apixaban.
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 |
|---|---|---|
| ApixabanApixaban is an anticoagulant that works by inhibiting the coagulation factor, Factor Xa. | Drug | Apixaban for HIT, Apixaban for HITT |
Primary outcome
Cumulative Incidence of New Symptomatic Thromboembolic Complications (TEC) Within 30 Days of the Initiation of Apixaban
Time frame: 30 days
New TEC
7 secondary outcomes
Composite Cumulative Incidence of All-cause Mortality, Limb Amputation and New TEC
Time frame: From the start of treatment until 30 days after the end of treatment, up to 60 days total for participants with HIT and up to 120 days total for participants with HITT
Composite Cumulative Incidence of New TEC and Major Bleeding
Time frame: From the start of treatment until 30 days after the end of treatment, up to 60 days total for participants with HIT and up to 120 days total for participants with HITT
Cumulative Incidence of Major Bleeding
Time frame: From the start of treatment until 30 days after the end of treatment, up to 60 days total for participants with HIT and up to 120 days total for participants with HITT
Time to Platelet Recovery
Time frame: From the start of treatment until time of platelet recovery, up to 60 days total for participants with HIT and up to 120 days total for participants with HITT
Cumulative Incidence of All Cause Mortality
Time frame: From the start of treatment until the time of death or until 30 days after the end of treatment, up to 60 days total for participants with HIT and up to 120 days total for participants with HITT
Cumulative Incidence of Limb Amputation
Time frame: From the start of treatment until 30 days after the end of treatment, up to 60 days total for participants with HIT and up to 120 days total for participants with HITT
Cumulative Incidence of New Thromboembolic Complications (TEC)
Time frame: From the start of treatment until 30 days after the end of treatment, up to 60 days total for participants with HIT and up to 120 days total for participants with HITT
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Heparin-induced Thrombocytopenia
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Heparin-induced Thrombocytopenia
Recruiting
Characterization and Quantification of Platelet/Leukocyte Aggregates in Patients With Suspected Heparin-induced Thrombocytopenia
Heparin-induced Thrombocytopenia, HIT
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.
Rachel P Rosovsky, MD principal investigator
Massachusetts General Hospital
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Apixaban in people with Heparin-induced Thrombocytopenia and Heparin-induced Thrombocytopenia and Thrombosis, run by Massachusetts General Hospital at 3 sites 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 28 inclusion and 22 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: stopped early, as of the sponsor's last update on 23 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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. 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?
Yes. Results are posted in the registry (first posted 23 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Cumulative Incidence of New Symptomatic Thromboembolic Complications (TEC) Within 30 Days of the Initiation of Apixaban (time frame: 30 days). 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 23 Dec 2020.