Vaso-occlusive CrisisPhase 3NCT02179177
Apixaban in Patients With Sickle Cell Disease
A Phase 3 study testing Apixaban in people with Vaso-occlusive Crisis and Reduction in Hospitalizations, run by Nirmish Shah at 1 site in United States.
Trial summary
In patients with SCD, the use of low dose anticoagulation as an outpatient may lead to a significant decrease in morbidity and as a result, decrease healthcare utilization and costs. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Vaso-occlusive Crisis, Reduction in Hospitalizations, Sickle Cell Disease
- What is being tested?
- Apixaban
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2015to 3 Sep 2017
- Phase
- Phase 3
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- documented HgbSS, SC or HgbS-beta0 thalassemia,
- age ≥18 years old and ≤80,
- seen in outpatient clinic ≥2 times in past year
- seen for an acute care visit (hospitalization, emergency department, or day hospital visit) for pain >2 times in the past year.
Who cannot join
- Hospitalization or day hospital visit for pain crisis within the past 2 weeks
- Patients with ≥10 acute care visits within the past year will be excluded
- Creatinine >3.0 mg/dL
- creatinine ≥1.5 mg/dL AND weight ≤60 kg
- chronic use of antiplatelet or anticoagulation medication
- Patients with known vasculopathy or Moya-Moya
Show all 11Show fewer
- platelet count <100 X 109/L
- AST or ALT >3 times normal
- chronic red blood cell transfusions (scheduled transfusions)
- packed red blood cell transfusion within the past 2 months
- Use of CYP3A4 and P-gp inhibitor medications
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
Official title: Impact of Daily Prophylaxis Dose Anticoagulation With a Factor Xa Inhibitor (Apixaban) in Patients With Sickle Cell Disease
In patients with SCD, the use of low dose anticoagulation as an outpatient may lead to a significant decrease in morbidity and as a result, decrease healthcare utilization and costs. This study attempts to critically avoid admissions by reducing daily pain scores and pain crisis as an outpatient by use of a novel oral anticoagulant.
Read the detailed description
There is not only significant morbidity associated with patients with SCD, but also costs associated with the numerous hospitalizations. Small studies have been unable to show clear benefit of the use of low dose anticoagulation in SCD due to limited sample size or the inclusion of very specific populations. However, studies have shown a decrease in the level of elevated prothrombotic markers with anticoagulation, and one study using full dose anticoagulation in patients with a generally milder form of SCD (with high protective hemoglobin) showed more rapid decrease in clinical pain with use of anticoagulation, suggesting a possible benefit of such therapy. Due to the paucity of data to support therapeutic dose LMWH in the more severe forms of SCD seen in the United States, we have chosen prophylactic dose anticoagulation. This study proposal attempts to critically avoid admissions by reducing daily pain scores and pain crisis as an outpatient by use of a novel oral anticoagulant.
The development of novel anticoagulants such as oral direct factor Xa (FXa) inhibitors allows the realistic use of daily prophylactic dosing as an outpatient. Past studies as detailed earlier have been limited by attempts to use subcutaneous injections or frequent, close monitoring for acenocoumarol treatment, both which are not ideal for chronic daily use. Furthermore, the use of global assays such calibrated automated thrombography (CAT) have shown further details about thrombin generation in a population which is hypercoagulable at baseline.
This is a double blind, parallel group, placebo controlled feasibility study with an enrollment target of 25 patients (12 per arm). All subjects that meet inclusion criteria as an outpatient, following a 1 month observation, will be randomized to receive an oral prophylactic dose factor Xa inhibitor (Apixaban 2.5mg po bid) or placebo for 6 months. Subjects will return for a 30 day (+/- 5 days) follow-up visit after the End of Treatment (EOT) visit. Initial randomization will occur by computerized randomization technique by the investigational drug services (IDS) at Duke University Medical Center.
- Being tested
- Apixaban, Placebo
- Keywords
- Vaso-occlusive crisis, Reduction in hospitalizations, Sickle Cell Disease
- Medical subject headings
- Vaso-Occlusive Crises, Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ApixabanDrug
Drug is taken by mouth twice a day for 6 months
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Apixaban | Active comparator | Active drug Apixaban 2.5mg taken by mouth twice a day Receives: Drug: Apixaban |
| Placebo | Placebo comparator | Sugar pills that look like Apixaban that will be taken by mouth twice a day Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Pain as Measured by Visual Analog Scale (VAS)
The primary pain assessment tool will be a 10-cm horizontal visual analog scale (VAS), with "0" corresponding to no pain at one end and "10" indicating the worst pain at the other.
Measured: Month 1 to Month 8
Secondary outcomes (3)
Change in Thrombin Generation Using D-dimer Measurement as a Surrogate
Measured: Enrollment to 2 months
Daily Pain Scores While Hospitalized as Measured by VAS
The primary pain assessment tool will be a 10-cm horizontal visual analog scale (VAS), with "0" corresponding to no pain at one end and "10" indicating the worst pain at the other. Secondary analysis will be performed to evaluate differences when patients are hospitalized and on study drug versus placebo.
Measured: up to 8 months
Number of Hospitalizations During Treatment
Measured: up to 8 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2014 (estimated)
- Study startJan 2015
- Primary completion3 Sep 2017
- Study completion3 Sep 2017
Why it stopped: funding has been exhausted
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 Vaso-occlusive CrisisStudies 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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nirmish Shah
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor-investigator, Nirmish Shah, Duke University
- Investigators
- Nirmish Shah, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02179177
- Sponsor's protocol ID
- Pro00048953
- Status last verified
- Feb 2020
- First submitted
- 27 Jun 2014
- Last updated
- 11 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Daily Prophylaxis Dose Anticoagulation With a Factor Xa Inhibitor (Apixaban) in Patients With Sickle Cell Disease
- ClinicalTrials.gov ID
- NCT02179177
- Acronym / sponsor ID
- Pro00048953
- Keywords
- Vaso-occlusive crisis, Reduction in hospitalizations, Sickle Cell Disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: funding has been exhausted
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Nirmish ShahUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- Jan 2015
- Primary completion
- 3 Sep 2017 (actual)
- Study completion
- 3 Sep 2017 (actual)
- First posted
- 1 Jul 2014 (estimated)
- Results
- Posted 11 Mar 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In patients with SCD, the use of low dose anticoagulation as an outpatient may lead to a significant decrease in morbidity and as a result, decrease healthcare utilization and costs. This study attempts to critically avoid admissions by reducing daily pain scores and pain crisis as an outpatient by use of a novel oral anticoagulant.
Detailed description
There is not only significant morbidity associated with patients with SCD, but also costs associated with the numerous hospitalizations. Small studies have been unable to show clear benefit of the use of low dose anticoagulation in SCD due to limited sample size or the inclusion of very specific populations. However, studies have shown a decrease in the level of elevated prothrombotic markers with anticoagulation, and one study using full dose anticoagulation in patients with a generally milder form of SCD (with high protective hemoglobin) showed more rapid decrease in clinical pain with use of anticoagulation, suggesting a possible benefit of such therapy. Due to the paucity of data to support therapeutic dose LMWH in the more severe forms of SCD seen in the United States, we have chosen prophylactic dose anticoagulation. This study proposal attempts to critically avoid admissions by reducing daily pain scores and pain crisis as an outpatient by use of a novel oral anticoagulant.
The development of novel anticoagulants such as oral direct factor Xa (FXa) inhibitors allows the realistic use of daily prophylactic dosing as an outpatient. Past studies as detailed earlier have been limited by attempts to use subcutaneous injections or frequent, close monitoring for acenocoumarol treatment, both which are not ideal for chronic daily use. Furthermore, the use of global assays such calibrated automated thrombography (CAT) have shown further details about thrombin generation in a population which is hypercoagulable at baseline.
This is a double blind, parallel group, placebo controlled feasibility study with an enrollment target of 25 patients (12 per arm). All subjects that meet inclusion criteria as an outpatient, following a 1 month observation, will be randomized to receive an oral prophylactic dose factor Xa inhibitor (Apixaban 2.5mg po bid) or placebo for 6 months. Subjects will return for a 30 day (+/- 5 days) follow-up visit after the End of Treatment (EOT) visit. Initial randomization will occur by computerized randomization technique by the investigational drug services (IDS) at Duke University Medical Center.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Apixaban | Active comparator | Drug: ApixabanActive drug Apixaban 2.5mg taken by mouth twice a day |
| Placebo | Placebo comparator | Drug: PlaceboSugar pills that look like Apixaban that will be taken by mouth twice a day |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- documented HgbSS, SC or HgbS-beta0 thalassemia,
- age ≥18 years old and ≤80,
- seen in outpatient clinic ≥2 times in past year
- seen for an acute care visit (hospitalization, emergency department, or day hospital visit) for pain >2 times in the past year.
Key exclusion criteria (11 listed)
- Hospitalization or day hospital visit for pain crisis within the past 2 weeks
- Patients with ≥10 acute care visits within the past year will be excluded
- Creatinine >3.0 mg/dL
- creatinine ≥1.5 mg/dL AND weight ≤60 kg
- chronic use of antiplatelet or anticoagulation medication
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 |
|---|---|---|
| ApixabanDrug is taken by mouth twice a day for 6 months | Drug | Apixaban |
| Placebo | Drug | Placebo |
Primary outcome
Change in Pain as Measured by Visual Analog Scale (VAS)
Time frame: Month 1 to Month 8
The primary pain assessment tool will be a 10-cm horizontal visual analog scale (VAS), with "0" corresponding to no pain at one end and "10" indicating the worst pain at the other.
3 secondary outcomes
Change in Thrombin Generation Using D-dimer Measurement as a Surrogate
Time frame: Enrollment to 2 months
Daily Pain Scores While Hospitalized as Measured by VAS
Time frame: up to 8 months
Number of Hospitalizations During Treatment
Time frame: up to 8 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Vaso-occlusive Crisis
Not yet recruitingPhase 1
Buprenorphine for the Management of Pain in Children With Sickle Cell Disease
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RecruitingPhase 2
Safety of Anumigilimab (CSL324) in Adults With Sickle Cell Disease (SCD)
Sickle Cell Disease
Not yet recruiting
Hypoxic Red Blood Cells in Sickle Cell Anemia
Sickle Cell Anaemia, Sickle Cell Anemia Crisis
Recruiting
Virtual Reality for SCD VOC
Sickle Cell Disease
RecruitingPhase 3
A Study to Investigate the Efficacy and Safety of Crizanlizumab (5 mg/kg) Compared With Placebo in Adolescent and Adult Sickle Cell Disease Patients Who Experience Frequent Vaso-Occlusive Crises (SPARKLE)
Sickle Cell Disease
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.
Nirmish Shah, MD principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Apixaban in people with Vaso-occlusive Crisis and Reduction in Hospitalizations, run by Nirmish Shah 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 4 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: stopped early, as of the sponsor's last update on 11 Mar 2020. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 11 Mar 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?
Change in Pain as Measured by Visual Analog Scale (VAS) (time frame: Month 1 to Month 8). 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 11 Mar 2020.