Sickle Cell DiseaseNCT04349189
Venous Thrombosis Biomarkers in Sickle Cell Disease and Sickle Cell Trait
An observational study of Sickle Cell Disease and Venous Thrombosis, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
Background: Venous thromboembolism (VTE) includes the abnormal clotting of blood in a deep vein of the upper or lower limbs (deep vein thrombosis) that may travel to and block a blood vessel in the lung (pulmonary embolism). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Sickle Cell Disease, Venous Thrombosis, Sickle Cell Trait
- How many people
- 119 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2020to 20 Jun 2024
- Phase
- Observational
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: The natural history of SCD 04-H-0161 protocol (NCT00081523) will specifically be leveraged to recruit participants with VTE. In this study we will assess feasibility of establishing a prospective natural history study of thrombosis in SCD. Establishing feasibility could lead to recruitment of SCD patients experiencing thrombosis, particularly those that are understudied including patients with HbSC disease.
Who may be able to join
- Sickle cell disease with and without VTE
- Sickle cell disease (HbSS, HbSC and HbS/beta-thalassemia genotypes) in steady state.
- Diagnosis of at least one or more VTE within 5 years of study enrolment confirmed by radiologic imaging (for SCD patients with VTE).
- Absence of clinical history of VTE (for SCD controls)
- Between 18 and 80 years of age.
- Ability to provide informed written consent.
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- Sickle cell trait
- Sickle cell disease (HbAS genotype).
- Absence of clinical history of VTE
- Between 18 and 80 years of age.
- Ability to provide informed written consent.
- Ethnically matched controls
- Between 18 and 80 years of age.
- African, or of African descent.
- Ability to provide informed written consent.
- Absence of clinical history of VTE
Who cannot join
- SCD with and without VTE
- Pregnancy (test done at enrollment; if a subject becomes pregnant during the study period, samples will not be obtained while the subject is pregnant and the subject will be taken off study).
- Patients on exchange transfusion or having received a simple blood transfusion in the past 60 days.
- Active viral infection as evidenced by testing positive for hepatitis B surface antigen or hepatitis C virus (HCV) antibody (Ab) with signs of active hepatitis B or C virus infection. If the subject is positive for HCV Ab, a reverse transcriptasepolymerase chain reaction test will be conducted. Subjects with hepatitis C may be rescreened after receiving appropriate hepatitis C treatment.
- Testing positive for human immunodeficiency virus 1 or 2 Ab with evidence for ongoing active infection (i.e., CD 4 count <400/microL and viral load >100,000 copies/ml) on antiretroviral therapy.
- Active acute inflammatory disorders rheumatoid arthritis or systemic lupus erythematosus on disease modifying therapy.
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- Diabetes mellitus judged to be under poor control by the Investigator evidenced by a single fasting sugar value >250gm/dl or requiring >3 antidiabetic agents, including insulin (all insulins are considered 1 agent); use of insulin per se is not exclusionary.
- SCT and ethnically matched controls
- Diagnosis of any of the following chronic disease or conditions: Sickle cell disease (HbSS, HbSC and HbS/beta-thalassemia genotypes).
- Clinical history of VTE.
- Pregnancy (test done at enrollment; if a subject becomes pregnant during the study period, samples will not be obtained while the subject is pregnant and the subject will be taken off study.
- Active viral infection as evidenced by testing positive for hepatitis B surface antigen or hepatitis C virus (HCV) antibody (Ab) with signs of active hepatitis B or C virus infection. If the subject is positive for HCV Ab, a reverse transcriptasepolymerase chain reaction test will be conducted. Subjects with hepatitis C may be rescreened after receiving appropriate hepatitis C treatment.
- Testing positive for human immunodeficiency virus 1 or 2 Ab with evidence for ongoing active infection (i.e., CD 4 count <400/microL and viral load >100,000 copies/ml) on antiretroviral therapy.
- Active acute inflammatory disorders rheumatoid arthritis or systemic lupus erythematosus on disease modifying therapy.
- Diabetes mellitus judged to be under poor control by the Investigator evidenced by a single fasting sugar value >250gm/dl or requiring >3 antidiabetic agents, including insulin (all insulins are considered 1 agent); use of insulin per se is not exclusionary.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Background:
Venous thromboembolism (VTE) includes the abnormal clotting of blood in a deep vein of the upper or lower limbs (deep vein thrombosis) that may travel to and block a blood vessel in the lung (pulmonary embolism). Some people with sickle cell disease (SCD)-a red blood cell disorder-seem to be at greater risk for developing these blood clots. Researchers want to study the blood of people with SCD and VTE as well as healthy people to develop better treatments to prevent blood clots.
Read more
Objective:
To study blood clotting in SCD because it is the most common cause of vascular death after a heart attack or stroke.
Eligibility:
People ages 18-80 who have SCD (with or without a history of blood clots) or the trait for SCD, and healthy volunteers
Design:
Participants will be screened with medical history, physical exam, and medical records review. They will give blood samples.
Participants will have phone calls either every 3 months or once a year, for 2 years. They will give updates on their health. They may give additional medical records. The phone calls may last up to 30 minutes.
If participants have a VTE or pain crisis episode, they may visit the Clinical Center. These visits may last up to 4 hours. They will repeat the screening tests and give blood samples.
Some participants may be invited to take part in blood studies.
After 2 years, some participants will have a follow-up visit at the Clinical Center.
Participation will last for about 2 years.
Read the detailed description
Venous thromboembolism (VTE) the third most frequent cause of vascular mortality after myocardial infarction and stroke, occurs more frequently among Americans of African descent compared with other ethnic minorities in the US. VTEs are provoked by diverse risk factors but can be unprovoked in individuals with a hypercoagulable state, in whom there is a predisposition for thrombosis. Patients with Sickle Cell Disease (SCD) have added risk of VTE as the disease itself is a hypercoagulable state. VTE frequency is increased across the entire spectrum of SCD severity, in those experiencing both mild (HbSC patients) and severe sickling symptoms (HbSS/HbSbeta0 thalassemia patients). Studies show that up to 12% of patients with SCD have VTE events [deep vein thrombus (DVT) or pulmonary embolism (PE) or both] early in life by age 40, most of which are unprovoked. Moreover, owing to a persistent hypercoagulable state, SCD patients are at an unacceptably high risk for recurrence, particularly those in whom VTE was unprovoked. SCD patients who develop a VTE have a 24.1% risk of recurrence over 5 years. A history of a VTE in SCD is associated with greater mortality risk (Odd Ratio, OR = 2.88; Confidence Interval, CI = 2.35 - 3.52).
Our overall hypothesis is that the proinflammatory state associated with SCD perturbs the coagulation system and contributes to the thrombotic vascular pathobiology of SCD. Abnormal intravascular tissue factor expressed on monocytes and endothelial cells and circulating tissue factor positive extracellular vesicles released by these cells drive coagulation activation in SCD. Specifically, intravascular tissue factor forms the tenase complex (TF:VIIa) which converts factor X to factor Xa, generating the initial thrombin burst that possibly triggers intravascular thrombosis. Besides, heightened tissue factor exposure during acute sickling crises, increased release of tissue factor positive extracellular vesicles and inadequate clearance of the latter favors thrombin generation, fibrin deposition and thrombosis in the venous vasculature. SCD patients with VTE and/or recurrent VTE are therefore more likely to have more tissue factor positive extracellular vesicles and plasma tissue factor procoagulant activity compared with SCD patients without VTE.
Prospective cohort studies of extended duration/indefinite anticoagulation in non-SCD patients with an underlying hypercoagulable state have effectively reduced recurrence rates. However, similar studies of extended duration anticoagulation in SCD patients are lacking. Besides, whether exposing SCD patients to extended/indefinite anticoagulation increases bleeding risk to unacceptably high levels is unknown. Studying thrombogenic risk and specifically identifying those SCD patients who are at greatest risk for VTE recurrence therefore becomes a high priority. In addition, individuals with sickle cell trait are prone to thrombosis but few studies evaluate markers of thrombotic risk in these individuals. Such studies could provide a rationale for targeted primary or secondary VTE prophylaxis.
In the current proposal we will test the hypothesis that plasma tissue factor positive extracellular vesicles and tissue factor activity are elevated among SCD patients with VTE compared with SCD patients without VTE and in individuals with Sickle Cell Trait compared with ethnically matched controls.
- Conditions
- Sickle Cell Disease, Venous Thrombosis, Sickle Cell Trait, Hypercoagulable State, Venous Thromboembolism
- Keywords
- hypercoagulable state, Recurrence, Biomarkers, Venous Thromboembolism, Vascular Mortality, Natural History
- Medical subject headings
- Anemia, Sickle Cell, Venous Thrombosis, Sickle Cell Trait, Thrombophilia, Venous Thromboembolism, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | 50 Men and Women with sickle cell disease and VTE | |
| Group 2 | 50 Men and Women with sickle cell disease but no VTE | |
| Group 3 | 50 Men and Women with sickle cell trait | |
| Group 4 | 50 ethnically matched Men and Women without sickle cell disease, sickle cell trait, or VTE |
What is being measured
The primary outcome is the main question the study is designed to answer.
tissue factor positive
Number of tissue factor positive EVs/ml of plasma
Measured: At baseline during study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2020
- Study start1 Sep 2020
- Primary completion20 Jun 2024
- Study completion20 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The 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
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 119 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- John F Tisdale, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04349189
- Sponsor's protocol ID
- 200068
- Other IDs
- 20-H-0068
- Status last verified
- 9 Jun 2026
- First submitted
- 15 Apr 2020
- Last updated
- 12 Jun 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Undecided: It is not yet known if there will be a plan to make IPD available
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Venous Thrombosis Biomarkers in Sickle Cell Disease and Sickle Cell Trait
- ClinicalTrials.gov ID
- NCT04349189
- Acronym / sponsor ID
- 200068
- Conditions
- Sickle Cell Disease, Venous Thrombosis, Sickle Cell Trait, Hypercoagulable State, Venous Thromboembolism
- Keywords
- hypercoagulable state, Recurrence, Biomarkers, Venous Thromboembolism, Vascular Mortality, Natural History
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 119 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 1 Sep 2020 (actual)
- Primary completion
- 20 Jun 2024 (actual)
- Study completion
- 20 Jun 2024 (actual)
- First posted
- 16 Apr 2020 (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.
Background:
Venous thromboembolism (VTE) includes the abnormal clotting of blood in a deep vein of the upper or lower limbs (deep vein thrombosis) that may travel to and block a blood vessel in the lung (pulmonary embolism). Some people with sickle cell disease (SCD)-a red blood cell disorder-seem to be at greater risk for developing these blood clots. Researchers want to study the blood of people with SCD and VTE as well as healthy people to develop better treatments to prevent blood clots.
Objective:
To study blood clotting in SCD because it is the most common cause of vascular death after a heart attack or stroke.
Eligibility:
People ages 18-80 who have SCD (with or without a history of blood clots) or the trait for SCD, and healthy volunteers
Design:
Participants will be screened with medical history, physical exam, and medical records review. They will give blood samples.
Participants will have phone calls either every 3 months or once a year, for 2 years. They will give updates on their health. They may give additional medical records. The phone calls may last up to 30 minutes.
If participants have a VTE or pain crisis episode, they may visit the Clinical Center. These visits may last up to 4 hours. They will repeat the screening tests and give blood samples.
Some participants may be invited to take part in blood studies.
After 2 years, some participants will have a follow-up visit at the Clinical Center.
Participation will last for about 2 years.
Detailed description
Venous thromboembolism (VTE) the third most frequent cause of vascular mortality after myocardial infarction and stroke, occurs more frequently among Americans of African descent compared with other ethnic minorities in the US. VTEs are provoked by diverse risk factors but can be unprovoked in individuals with a hypercoagulable state, in whom there is a predisposition for thrombosis. Patients with Sickle Cell Disease (SCD) have added risk of VTE as the disease itself is a hypercoagulable state. VTE frequency is increased across the entire spectrum of SCD severity, in those experiencing both mild (HbSC patients) and severe sickling symptoms (HbSS/HbSbeta0 thalassemia patients). Studies show that up to 12% of patients with SCD have VTE events [deep vein thrombus (DVT) or pulmonary embolism (PE) or both] early in life by age 40, most of which are unprovoked. Moreover, owing to a persistent hypercoagulable state, SCD patients are at an unacceptably high risk for recurrence, particularly those in whom VTE was unprovoked. SCD patients who develop a VTE have a 24.1% risk of recurrence over 5 years. A history of a VTE in SCD is associated with greater mortality risk (Odd Ratio, OR = 2.88; Confidence Interval, CI = 2.35 - 3.52).
Our overall hypothesis is that the proinflammatory state associated with SCD perturbs the coagulation system and contributes to the thrombotic vascular pathobiology of SCD. Abnormal intravascular tissue factor expressed on monocytes and endothelial cells and circulating tissue factor positive extracellular vesicles released by these cells drive coagulation activation in SCD. Specifically, intravascular tissue factor forms the tenase complex (TF:VIIa) which converts factor X to factor Xa, generating the initial thrombin burst that possibly triggers intravascular thrombosis. Besides, heightened tissue factor exposure during acute sickling crises, increased release of tissue factor positive extracellular vesicles and inadequate clearance of the latter favors thrombin generation, fibrin deposition and thrombosis in the venous vasculature. SCD patients with VTE and/or recurrent VTE are therefore more likely to have more tissue factor positive extracellular vesicles and plasma tissue factor procoagulant activity compared with SCD patients without VTE.
Prospective cohort studies of extended duration/indefinite anticoagulation in non-SCD patients with an underlying hypercoagulable state have effectively reduced recurrence rates. However, similar studies of extended duration anticoagulation in SCD patients are lacking. Besides, whether exposing SCD patients to extended/indefinite anticoagulation increases bleeding risk to unacceptably high levels is unknown. Studying thrombogenic risk and specifically identifying those SCD patients who are at greatest risk for VTE recurrence therefore becomes a high priority. In addition, individuals with sickle cell trait are prone to thrombosis but few studies evaluate markers of thrombotic risk in these individuals. Such studies could provide a rationale for targeted primary or secondary VTE prophylaxis.
In the current proposal we will test the hypothesis that plasma tissue factor positive extracellular vesicles and tissue factor activity are elevated among SCD patients with VTE compared with SCD patients without VTE and in individuals with Sickle Cell Trait compared with ethnically matched controls.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group 1 | – | –50 Men and Women with sickle cell disease and VTE |
| Group 2 | – | –50 Men and Women with sickle cell disease but no VTE |
| Group 3 | – | –50 Men and Women with sickle cell trait |
| Group 4 | – | –50 ethnically matched Men and Women without sickle cell disease, sickle cell trait, or VTE |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The natural history of SCD 04-H-0161 protocol (NCT00081523) will specifically be leveraged to recruit participants with VTE. In this study we will assess feasibility of establishing a prospective natural history study of thrombosis in SCD. Establishing feasibility could lead to recruitment of SCD patients experiencing thrombosis, particularly those that are understudied including patients with HbSC disease.
Key inclusion criteria (16 listed)
- Sickle cell disease with and without VTE
- Sickle cell disease (HbSS, HbSC and HbS/beta-thalassemia genotypes) in steady state.
- Diagnosis of at least one or more VTE within 5 years of study enrolment confirmed by radiologic imaging (for SCD patients with VTE).
- Absence of clinical history of VTE (for SCD controls)
- Between 18 and 80 years of age.
Key exclusion criteria (15 listed)
- SCD with and without VTE
- Pregnancy (test done at enrollment; if a subject becomes pregnant during the study period, samples will not be obtained while the subject is pregnant and the subject will be taken off study).
- Patients on exchange transfusion or having received a simple blood transfusion in the past 60 days.
- Active viral infection as evidenced by testing positive for hepatitis B surface antigen or hepatitis C virus (HCV) antibody (Ab) with signs of active hepatitis B or C virus infection. If the subject is positive for HCV Ab, a reverse transcriptasepolymerase chain reaction test will be conducted. Subjects with hepatitis C may be rescreened after receiving appropriate hepatitis C treatment.
- Testing positive for human immunodeficiency virus 1 or 2 Ab with evidence for ongoing active infection (i.e., CD 4 count <400/microL and viral load >100,000 copies/ml) on antiretroviral therapy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
tissue factor positive
Time frame: At baseline during study
Number of tissue factor positive EVs/ml of plasma
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided. Undecided: It is not yet known if there will be a plan to make IPD available
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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.
John F Tisdale, M.D. principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Sickle Cell Disease and Venous Thrombosis, run by National Heart, Lung, and Blood Institute (NHLBI) 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 16 inclusion and 15 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: finished, as of the sponsor's last update on 12 Jun 2026. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
tissue factor positive (time frame: At baseline during study). 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 12 Jun 2026.