Clinical trial NCT03594045: Efficacy and Safety of Apixaban in the Treatment of Heparin Induced Thrombocytopenia (HIT)
Official title: A Phase II Study to Evaluate the Efficacy and Safety of Apixaban in the Treatment of Heparin Induced Thrombocytopenia (HIT)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Heparin-induced Thrombocytopenia
Heparin-induced Thrombocytopenia and Thrombosis
Keywords: Heparin-induced Thrombocytopenia
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2018-07-20
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

* 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
* 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.

Exclusion Criteria:

* 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.
* 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.

Primary outcomes:
measure: Cumulative Incidence of New Symptomatic Thromboembolic Complications (TEC) Within 30 Days of the Initiation of Apixaban
timeFrame: 30 days
Secondary outcomes:
measure: Composite Cumulative Incidence of All-cause Mortality, Limb Amputation and New TEC
timeFrame: 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
measure: Composite Cumulative Incidence of New TEC and Major Bleeding
timeFrame: 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
measure: Cumulative Incidence of Major Bleeding
timeFrame: 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
measure: Time to Platelet Recovery
timeFrame: 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
measure: Cumulative Incidence of All Cause Mortality
timeFrame: 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
measure: Cumulative Incidence of Limb Amputation
timeFrame: 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
measure: Cumulative Incidence of New Thromboembolic Complications (TEC)
timeFrame: 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
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Rachel P Rosovsky, MD
role: PRINCIPAL_INVESTIGATOR
References: