The Effect of Rivaroxaban in Sickle Cell Disease

• ClinicalTrials.gov Identifier: NCT02072668
• Recruitment Status: Completed
• First Posted: February 26, 2014
• Results First Posted: April 13, 2020
• Last Update Posted: April 13, 2020
• Sponsor: University of North Carolina, Chapel Hill
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): University of North Carolina, Chapel Hill

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Conditions: Sickle Cell Anemia; Sickle Cell-Beta0-Thalassemia
• Interventions: Drug: rivaroxaban; Drug: placebo
• Enrollment: 14

Participant Flow

Recruitment Details
Pre-assignment Details	15 subjects signed informed consent and were successfully screened. One subject withdrew during Baseline and prior to the first intervention and data from this individual are included in the baseline characteristics. One subject entered the second intervention period but was lost to follow up before receiving the intervention.

Arm/Group Title	Rivaroxaban, Then Placebo	Placebo, Then Rivaroxaban
Arm/Group Description	Participants first received Rivaroxaban 20 mg tablet once daily for 4 weeks. After a washout period of 2 weeks, they then received placebo (matching Rivaroxaban 20 mg tablet) once daily for 4 weeks. Rivaroxaban: 20 mg tablet by mouth daily for 4 weeks Placebo: Matching placebo tablet by mouth daily for 4 weeks	Participants first received placebo (matching Rivaroxaban 20 mg tablet) once daily for 4 weeks. After a washout period of 2 weeks, they then received Rivaroxaban 20 mg tablet once daily for 4 weeks. Rivaroxaban: 20 mg tablet by mouth daily for 4 weeks Placebo: Matching placebo tablet by mouth daily for 4 weeks
Period Title: First Intervention
Started	7	7
Completed	7	7
Not Completed	0	0
Period Title: Washout (2 Weeks)
Started	7	7
Completed	7	7
Not Completed	0	0
Period Title: Second Intervention
Started	7	7
Completed	6	7
Not Completed	1	0
Reason Not Completed
Lost to Follow-up	1	0

Baseline Characteristics

Arm/Group Title		Study Participants
Arm/Group Description		Participants who had a screening visit
Overall Number of Baseline Participants		15
Baseline Analysis Population Description		All participants who had a screening visit
Age, Customized; Mean (Standard Deviation); Unit of measure: Years
Age	Number Analyzed	15 participants
		39.00 (10.95)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	15 participants
	Female	9 60.0%
	Male	6 40.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	15 participants
	American Indian or Alaska Native	0 0.0%
	Asian	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	15 100.0%
	White	0 0.0%
	More than one race	0 0.0%
	Unknown or Not Reported	0 0.0%
Weight; Mean (Standard Deviation); Unit of measure: Kg
	Number Analyzed	15 participants
		68.22 (11.69)
Height [1]; Mean (Standard Deviation); Unit of measure: Cm
	Number Analyzed	14 participants
		169.40 (10.56)
		[1] Measure Analysis Population Description: Only measured on the participants who received study medication
White Blood Cell (WBC) count; Mean (Standard Deviation); Unit of measure: 10^9 cells/L
	Number Analyzed	15 participants
		8.49 (2.03)
Genotype - Hemoglobin SS (HbSS); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	15 participants
		15 100.0%
Platelet count; Mean (Standard Deviation); Unit of measure: 10^9 cells/L
	Number Analyzed	15 participants
		370.07 (169.13)
Serum Creatinine; Mean (Standard Deviation); Unit of measure: mg/dL
	Number Analyzed	15 participants
		0.7 (0.22)
Prothrombin Time (PT) [1] [2]; Mean (Standard Deviation); Unit of measure: Sec
	Number Analyzed	14 participants
		12.54 (0.99)
		[1] Measure Description: A test that measures how quickly blood clots; [2] Measure Analysis Population Description: Only measured on the participants who received study medication
International Normalized Ratio (INR) [1] [2]; Mean (Standard Deviation); Unit of measure: Ratio
	Number Analyzed	14 participants
		1.13 (0.09)
		[1] Measure Description: The ratio of a patient's prothrombin time to a normal (control) sample; [2] Measure Analysis Population Description: Only measured on the participants who received study medication
Partial Thromboplastin Time (PTT) [1] [2]; Mean (Standard Deviation); Unit of measure: Sec
	Number Analyzed	14 participants
		27.16 (2.48)
		[1] Measure Description: Measures the time it takes for a blood clot to form; [2] Measure Analysis Population Description: Only measured on the participants who received study medication

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to 4 Weeks in Soluble Vascular Cell Adhesion Molecule-1 (VCAM-1)
Description	Assay performed for soluble VCAM-1 using a commercially available enzyme-linked immunosorbent assay (ELISA).
Time Frame	Baseline, 4 weeks

Outcome Measure Data

Analysis Population Description

Data reported only for those participants who completed both interventions.

Arm/Group Title	Rivaroxaban	Placebo
Arm/Group Description:	Participants who received Rivaroxaban 20 mg tablet in either the first or the second half of the study	Participants who received placebo tablet (matching Rivaroxaban 20 mg) in either the first or the second half of the study
Overall Number of Participants Analyzed	13	13
Mean (95% Confidence Interval); Unit of Measure: pg/mL
	40.9; (-115.5 to 197.2)	10.7; (-84.5 to 105.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6281
	Comments	[Not Specified]
	Method	Student t-test followed by ANOVA
	Comments	Student t-test subsequently followed by crossover ANOVA model testing carry-over effect and treatment effect

2. Primary Outcome

Title	Change From Baseline to 4 Weeks in Interleukin-6 (IL-6)
Description	Assay performed for IL-6 using a commercially available enzyme-linked immunosorbent assay (ELISA).
Time Frame	Baseline, 4 weeks

Outcome Measure Data

Analysis Population Description

Data reported only for those participants who completed both interventions.

Arm/Group Title	Rivaroxaban	Placebo
Arm/Group Description:	Participants who received Rivaroxaban 20 mg tablet in either the first or the second half of the study	Participants who received placebo tablet (matching Rivaroxaban 20 mg) in either the first or the second half of the study
Overall Number of Participants Analyzed	13	13
Mean (95% Confidence Interval); Unit of Measure: pg/mL
	-1.1; (-4.47 to 2.28)	-0.54; (-1.69 to 0.62)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.7973
	Comments	[Not Specified]
	Method	Student t-test followed by ANOVA
	Comments	Student t-test subsequently followed by crossover ANOVA model testing carry-over effect and treatment effect

3. Secondary Outcome

Title	Change From Baseline to Week 4 in the Plasma Marker of Inflammation IL-2
Description	Interleukin-2 (IL-2) was measured using Luminex MAP technology at the UNC core facility
Time Frame	Baseline, 4 weeks

Outcome Measure Data

Analysis Population Description

Data analyzed for the 13 participants completing both interventions but results for 6 participants in each group fell outside the standard curve and could not be extrapolated.

Arm/Group Title	Rivaroxaban	Placebo
Arm/Group Description:	Participants who received Rivaroxaban 20 mg tablet in either the first or the second half of the study	Participants who received placebo tablet (matching Rivaroxaban 20 mg) in either the first or the second half of the study
Overall Number of Participants Analyzed	7	7
Mean (95% Confidence Interval); Unit of Measure: pg/mL
	-1.14; (-4.13 to 1.85)	0.36; (-3.48 to 4.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4442
	Comments	[Not Specified]
	Method	Student t-test followed by ANOVA
	Comments	Student t-test subsequently followed by crossover ANOVA model testing carry-over effect and treatment effect

4. Secondary Outcome

Title	Change From Baseline to Week 4 in the Plasma Marker of Inflammation IL-8
Description	Interleukin-8 (IL-8) was measured using Luminex MAP technology at the UNC core facility
Time Frame	Baseline, 4 weeks

Outcome Measure Data

Analysis Population Description

Data analyzed for the 13 participants completing both interventions but results for 4 participants in the rivaroxaban group and 5 participants in the placebo group fell outside the standard curve and could not be extrapolated.

Arm/Group Title	Rivaroxaban	Placebo
Arm/Group Description:	Participants who received Rivaroxaban 20 mg tablet in either the first or the second half of the study	Participants who received placebo tablet (matching Rivaroxaban 20 mg) in either the first or the second half of the study
Overall Number of Participants Analyzed	9	8
Mean (95% Confidence Interval); Unit of Measure: pg/mL
	0.95; (-41.83 to 43.72)	-4.08; (-38.36 to 30.19)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2545
	Comments	[Not Specified]
	Method	Student t-test followed by ANOVA
	Comments	Student t-test subsequently followed by crossover ANOVA model testing carry-over effect and treatment effect

5. Secondary Outcome

Title	Change From Baseline to Week 4 in Plasma Marker of Inflammation hsCRP
Description	high sensitivity C-reactive protein (hsCRP) was measured using Luminex MAP technology at the UNC core facility.
Time Frame	Baseline, 4 weeks

Outcome Measure Data

Analysis Population Description

Biomarker evaluations were limited to IL-2 and IL-8 as those were thought more likely to reflect inflammation activation based on experience in recent studies.

Arm/Group Title	Rivaroxaban	Placebo
Arm/Group Description:	Participants who received Rivaroxaban 20 mg tablet in either the first or the second half of the study	Participants who received placebo tablet (matching Rivaroxaban 20 mg) in either the first or the second half of the study
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

6. Secondary Outcome

Title	Change From Baseline to Week 4 in Plasma Marker of Inflammation MPO
Description	myeloperoxidase (MPO) was measured using Luminex MAP technology at the UNC core facility.
Time Frame	Baseline, 4 weeks

Outcome Measure Data

Analysis Population Description

Biomarker evaluations were limited to IL-2 and IL-8 as those were thought more likely to reflect inflammation activation based on experience in recent studies.

Arm/Group Title	Rivaroxaban	Placebo
Arm/Group Description:	Participants who received Rivaroxaban 20 mg tablet in either the first or the second half of the study	Participants who received placebo tablet (matching Rivaroxaban 20 mg) in either the first or the second half of the study
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

7. Secondary Outcome

Title	Change From Baseline to Week 4 in Plasma Marker of Inflammation TNF-a
Description	tumor necrosis factor alpha (TNF-a) was measured using Luminex MAP technology at the UNC core facility.
Time Frame	Baseline, 4 weeks

Outcome Measure Data

Analysis Population Description

Biomarker evaluations were limited to IL-2 and IL-8 as those were thought more likely to reflect inflammation activation based on experience in recent studies.

Arm/Group Title	Rivaroxaban	Placebo
Arm/Group Description:	Participants who received Rivaroxaban 20 mg tablet in either the first or the second half of the study	Participants who received placebo tablet (matching Rivaroxaban 20 mg) in either the first or the second half of the study
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

8. Secondary Outcome

Title	Change From Baseline to Week 4 in Plasma Marker of Inflammation sPLA2
Description	secretory phospholipase A2 (sPLA2) was measured using Luminex MAP technology at the UNC core facility
Time Frame	Baseline, 4 weeks

Outcome Measure Data

Analysis Population Description

Biomarker evaluations were limited to IL-2 and IL-8 as those were thought more likely to reflect inflammation activation based on experience in recent studies.

Arm/Group Title	Rivaroxaban	Placebo
Arm/Group Description:	Participants who received Rivaroxaban 20 mg tablet in either the first or the second half of the study	Participants who received placebo tablet (matching Rivaroxaban 20 mg) in either the first or the second half of the study
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

9. Secondary Outcome

Title	Change From Baseline to Week 4 in Marker of Endothelial Cell (EC) Activation sICAM
Description	levels of soluble intracellular adhesion molecule (sICAM) were measured using a commercially available ELISA
Time Frame	Baseline, 4 weeks

Outcome Measure Data

Analysis Population Description

Biomarker evaluations were limited to VCAM-1 and IL-6 as those were thought more likely to reflect endothelial cell activation based on experience in recent studies.

Arm/Group Title	Rivaroxaban, Then Placebo	Placebo, Then Rivaroxaban
Arm/Group Description:	Participants first received Rivaroxaban 20 mg tablet once daily for 4 weeks. After a washout period of 2 weeks, they then received placebo (matching Rivaroxaban 20 mg tablet) once daily for 4 weeks. Rivaroxaban: 20 mg tablet by mouth daily for 4 weeks Placebo: Matching placebo tablet by mouth daily for 4 weeks	Participants first received placebo (matching Rivaroxaban 20 mg tablet) once daily for 4 weeks. After a washout period of 2 weeks, they then received Rivaroxaban 20 mg tablet once daily for 4 weeks. Rivaroxaban: 20 mg tablet by mouth daily for 4 weeks Placebo: Matching placebo tablet by mouth daily for 4 weeks
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

10. Secondary Outcome

Title	Change From Baseline to Week 4 in TH1
Description	Microvascular blood flow was measured using laser doppler velocimetry (LDV) assessments of post-occlusive reactive hyperemia (PORH). This was accomplished using the Perimed PF5001 Velocitometer (Stockholm, Sweden). Variable measured: time to half before hyperemia (TH1)
Time Frame	Baseline, 4 weeks

Outcome Measure Data

Analysis Population Description

All participants randomized to each treatment were analyzed.

Arm/Group Title	Rivaroxaban	Placebo
Arm/Group Description:	Participants who received Rivaroxaban 20 mg tablet in either the first or the second half of the study	Participants who received placebo tablet (matching Rivaroxaban 20 mg) in either the first or the second half of the study
Overall Number of Participants Analyzed	14	13
Mean (95% Confidence Interval); Unit of Measure: seconds
	0.84; (-0.79 to 2.47)	-0.51; (-2.72 to 1.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4374
	Comments	[Not Specified]
	Method	Student t-test followed by ANOVA
	Comments	Student t-test subsequently followed by crossover ANOVA model testing carry-over effect and treatment effect

11. Secondary Outcome

Title	Change From Baseline to Week 4 in TM
Description	Microvascular blood flow was measured using laser doppler velocimetry (LDV) assessments of post-occlusive reactive hyperemia (PORH). This was accomplished using the Perimed PF5001 Velocitometer (Stockholm, Sweden). Variable measured: time to max (TM)
Time Frame	Baseline, 4 weeks

Outcome Measure Data

Analysis Population Description

All participants randomized to each treatment were analyzed.

Arm/Group Title	Rivaroxaban	Placebo
Arm/Group Description:	Participants who received Rivaroxaban 20 mg tablet in either the first or the second half of the study	Participants who received placebo tablet (matching Rivaroxaban 20 mg) in either the first or the second half of the study
Overall Number of Participants Analyzed	14	13
Mean (95% Confidence Interval); Unit of Measure: seconds
	-0.97; (-5.71 to 3.77)	-2.01; (-6.82 to 2.81)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3470
	Comments	[Not Specified]
	Method	Student t-test followed by ANOVA
	Comments	Student t-test subsequently followed by crossover ANOVA model testing carry-over effect and treatment effect

12. Secondary Outcome

Title	Change From Baseline to Week 4 in AH
Description	Microvascular blood flow was measured using laser doppler velocimetry (LDV) assessments of post-occlusive reactive hyperemia (PORH). This was accomplished using the Perimed PF5001 Velocitometer (Stockholm, Sweden). Variable measured: hyperemia area (AH)
Time Frame	Baseline, 4 weeks

Outcome Measure Data

Analysis Population Description

All participants randomized to each treatment were analyzed.

Arm/Group Title	Rivaroxaban	Placebo
Arm/Group Description:	Participants who received Rivaroxaban 20 mg tablet in either the first or the second half of the study	Participants who received placebo tablet (matching Rivaroxaban 20 mg) in either the first or the second half of the study
Overall Number of Participants Analyzed	14	13
Mean (95% Confidence Interval); Unit of Measure: perfusion units*seconds
	128; (-373 to 628)	-1189; (-2597 to 218)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0755
	Comments	[Not Specified]
	Method	Student t-test followed by ANOVA
	Comments	Student t-test subsequently followed by crossover ANOVA model testing carry-over effect and treatment effect

13. Secondary Outcome

Title	Change in Ratio From Baseline to Week 4 in AH/AO
Description	Microvascular blood flow was measured using laser doppler velocimetry (LDV) assessments of post-occlusive reactive hyperemia (PORH). This was accomplished using the Perimed PF5001 Velocitometer (Stockholm, Sweden). Variables measured: hyperemia area (AH) and occlusion area (AO)
Time Frame	Baseline, 4 weeks

Outcome Measure Data

Analysis Population Description

All participants randomized to each treatment were analyzed.

Arm/Group Title	Rivaroxaban	Placebo
Arm/Group Description:	Participants who received Rivaroxaban 20 mg tablet in either the first or the second half of the study	Participants who received placebo tablet (matching Rivaroxaban 20 mg) in either the first or the second half of the study
Overall Number of Participants Analyzed	14	13
Mean (95% Confidence Interval); Unit of Measure: ratio of AH to AO
	0.05; (-0.46 to 0.57)	-0.81; (-2.05 to 0.42)

14. Secondary Outcome

Title	Change From Baseline to Week 4 in PF
Description	Microvascular blood flow was measured using laser doppler velocimetry (LDV) assessments of post-occlusive reactive hyperemia (PORH). This was accomplished using the Perimed PF5001 Velocitometer (Stockholm, Sweden). Variable measured: peak flow (PF)
Time Frame	Baseline, 4 weeks

Outcome Measure Data

Analysis Population Description

All participants randomized to each treatment were analyzed.

Arm/Group Title	Rivaroxaban	Placebo
Arm/Group Description:	Participants who received Rivaroxaban 20 mg tablet in either the first or the second half of the study	Participants who received placebo tablet (matching Rivaroxaban 20 mg) in either the first or the second half of the study
Overall Number of Participants Analyzed	14	13
Mean (95% Confidence Interval); Unit of Measure: perfusion units
	3.14; (-9.08 to 15.36)	-12.62; (-26.63 to 1.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0708
	Comments	[Not Specified]
	Method	Student t-test followed by ANOVA
	Comments	Student t-test subsequently followed by crossover ANOVA model testing carry-over effect and treatment effect

15. Secondary Outcome

Title	Change From Baseline to Week 4 in RF
Description	Microvascular blood flow was measured using laser doppler velocimetry (LDV) assessments of post-occlusive reactive hyperemia (PORH). This was accomplished using the Perimed PF5001 Velocitometer (Stockholm, Sweden). Variable measured: rest flow (RF)
Time Frame	Baseline, 4 weeks

Outcome Measure Data

Analysis Population Description

All participants randomized to each treatment were analyzed.

Arm/Group Title	Rivaroxaban	Placebo
Arm/Group Description:	Participants who received Rivaroxaban 20 mg tablet in either the first or the second half of the study	Participants who received placebo tablet (matching Rivaroxaban 20 mg) in either the first or the second half of the study
Overall Number of Participants Analyzed	14	13
Mean (95% Confidence Interval); Unit of Measure: perfusion units
	0.29; (-1.47 to 2.05)	-0.62; (-2.96 to 1.73)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4501
	Comments	[Not Specified]
	Method	Student t-test followed by ANOVA
	Comments	Student t-test subsequently followed by crossover ANOVA model testing carry-over effect and treatment effect

16. Secondary Outcome

Title	Change From Baseline to Week 4 in TAT
Description	Assay for thrombin antithrombin (TAT) complexes performed using commercially available enzyme-linked immunosorbent assay (ELISA).
Time Frame	Baseline, 4 weeks

Outcome Measure Data

Analysis Population Description

Data reported only for those participants who completed both interventions.

Arm/Group Title	Rivaroxaban	Placebo
Arm/Group Description:	Participants who received Rivaroxaban 20 mg tablet in either the first or the second half of the study	Participants who received placebo tablet (matching Rivaroxaban 20 mg) in either the first or the second half of the study
Overall Number of Participants Analyzed	13	13
Mean (95% Confidence Interval); Unit of Measure: ug/mL
	-34.44; (-69.4 to 0.53)	0.35; (-3.77 to 4.47)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0767
	Comments	[Not Specified]
	Method	Student t-test followed by ANOVA
	Comments	Student t-test subsequently followed by crossover ANOVA model testing carry-over effect and treatment effect

17. Secondary Outcome

Title	Change From Baseline to Week 4 in D-Dimer
Description	Assay for D--dimer is performed using commercially available enzyme-linked immunosorbent assay (ELISA).
Time Frame	Baseline, 4 weeks

Outcome Measure Data

Analysis Population Description

Data reported only for those participants who completed both interventions.

Arm/Group Title	Rivaroxaban	Placebo
Arm/Group Description:	Participants who received Rivaroxaban 20 mg tablet in either the first or the second half of the study	Participants who received placebo tablet (matching Rivaroxaban 20 mg) in either the first or the second half of the study
Overall Number of Participants Analyzed	13	13
Mean (95% Confidence Interval); Unit of Measure: ng/mL
	-471; (-1654 to 712)	-1035; (-3880 to 1810)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.7250
	Comments	[Not Specified]
	Method	Student t-test followed by ANOVA
	Comments	Student t-test subsequently followed by crossover ANOVA model testing carry-over effect and treatment effect

Adverse Events

Time Frame	Data collected from date of informed consent to end of study visit, approximately 3 months
Adverse Event Reporting Description	The safety analysis population includes all participants exposed to any study intervention evaluated in this study.
Arm/Group Title	Rivaroxaban		Placebo
Arm/Group Description	Participants who received Rivaroxaban 20 mg tablet in either the first or the second half of the study		Participants who received placebo tablet (matching Rivaroxaban 20 mg) in either the first or the second half of the study
All-Cause Mortality
	Rivaroxaban		Placebo
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/14 (0.00%)		0/13 (0.00%)
Serious Adverse Events
	Rivaroxaban		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/14 (7.14%)		1/13 (7.69%)
Blood and lymphatic system disorders
painful crisis with bacteremia †	0/14 (0.00%)	0	1/13 (7.69%)	1
Respiratory, thoracic and mediastinal disorders
pneumonia †	1/14 (7.14%)	1	0/13 (0.00%)	0
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Rivaroxaban		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/14 (57.14%)		7/13 (53.85%)
Blood and lymphatic system disorders
neutropenia †	1/14 (7.14%)	1	2/13 (15.38%)	3
Gastrointestinal disorders
diarrhea, nausea and vomiting †	2/14 (14.29%)	3	0/13 (0.00%)	0
elevate liver enzymes †	0/14 (0.00%)	0	1/13 (7.69%)	1
General disorders
headache †	2/14 (14.29%)	2	1/13 (7.69%)	1
chest pain †	3/14 (21.43%)	3	0/13 (0.00%)	0
insomnia †	1/14 (7.14%)	1	0/13 (0.00%)	0
dyspnea †	1/14 (7.14%)	1	0/13 (0.00%)	0
right flank pain †	1/14 (7.14%)	1	0/13 (0.00%)	0
Musculoskeletal and connective tissue disorders
back pain †	1/14 (7.14%)	1	1/13 (7.69%)	1
pain in lower extremities †	1/14 (7.14%)	1	1/13 (7.69%)	1
Renal and urinary disorders
pelvic pressure with urination †	1/14 (7.14%)	1	0/13 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
cough, fever, body aches, congestion †	1/14 (7.14%)	1	2/13 (15.38%)	2
Skin and subcutaneous tissue disorders
ankle laceration †	0/14 (0.00%)	0	1/13 (7.69%)	1
tick bite †	1/14 (7.14%)	1	0/13 (0.00%)	0
tinea versicolor †	1/14 (7.14%)	1	0/13 (0.00%)	0
Vascular disorders
pain crisis treated at home †	4/14 (28.57%)	6	2/13 (15.38%)	2
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Dr. Kenneth Ataga
• Organization: University of Tennessee Center for the Heath Sciences
• Phone: 901.448.3181
• EMail: kataga@uthsc.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ataga KI, Elsherif L, Wichlan D, Wogu AF, Matsui N, Pawlinski R, Cai J, Key NS. A pilot study of the effect of rivaroxaban in sickle cell anemia. Transfusion. 2021 Jun;61(6):1694-1698. doi: 10.1111/trf.16343. Epub 2021 Mar 4.

• Responsible Party: University of North Carolina, Chapel Hill
• ClinicalTrials.gov Identifier: NCT02072668
• Other Study ID Numbers: 12-2607; U01HL117659-01 ( U.S. NIH Grant/Contract )
• First Submitted: February 24, 2014
• First Posted: February 26, 2014
• Results First Submitted: March 18, 2020
• Results First Posted: April 13, 2020
• Last Update Posted: April 13, 2020