Trial Outcomes & Findings for The Effect of Rivaroxaban in Sickle Cell Disease (NCT NCT02072668)

NCT ID: NCT02072668

Last Updated: 2020-04-13

Results Overview

Assay performed for soluble VCAM-1 using a commercially available enzyme-linked immunosorbent assay (ELISA).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

14 participants

Primary outcome timeframe

Baseline, 4 weeks

Results posted on

2020-04-13

Participant Flow

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.

Participant milestones

Participant milestones
Measure
Rivaroxaban, Then Placebo
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
Placebo, Then Rivaroxaban
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
First Intervention
STARTED
7
7
First Intervention
COMPLETED
7
7
First Intervention
NOT COMPLETED
0
0
Washout (2 Weeks)
STARTED
7
7
Washout (2 Weeks)
COMPLETED
7
7
Washout (2 Weeks)
NOT COMPLETED
0
0
Second Intervention
STARTED
7
7
Second Intervention
COMPLETED
6
7
Second Intervention
NOT COMPLETED
1
0

Reasons for withdrawal

Reasons for withdrawal
Measure
Rivaroxaban, Then Placebo
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
Placebo, Then Rivaroxaban
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
Second Intervention
Lost to Follow-up
1
0

Baseline Characteristics

Only measured on the participants who received study medication

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Study Participants
n=15 Participants
Participants who had a screening visit
Age, Customized
Age
39.00 years
STANDARD_DEVIATION 10.95 • n=15 Participants
Sex: Female, Male
Female
9 Participants
n=15 Participants
Sex: Female, Male
Male
6 Participants
n=15 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=15 Participants
Race (NIH/OMB)
Asian
0 Participants
n=15 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=15 Participants
Race (NIH/OMB)
Black or African American
15 Participants
n=15 Participants
Race (NIH/OMB)
White
0 Participants
n=15 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=15 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=15 Participants
Weight
68.22 kg
STANDARD_DEVIATION 11.69 • n=15 Participants
Height
169.40 cm
STANDARD_DEVIATION 10.56 • n=14 Participants • Only measured on the participants who received study medication
White Blood Cell (WBC) count
8.49 10^9 cells/L
STANDARD_DEVIATION 2.03 • n=15 Participants
Genotype - Hemoglobin SS (HbSS)
15 Participants
n=15 Participants
Platelet count
370.07 10^9 cells/L
STANDARD_DEVIATION 169.13 • n=15 Participants
Serum Creatinine
0.7 mg/dL
STANDARD_DEVIATION 0.22 • n=15 Participants
Prothrombin Time (PT)
12.54 sec
STANDARD_DEVIATION 0.99 • n=14 Participants • Only measured on the participants who received study medication
International Normalized Ratio (INR)
1.13 ratio
STANDARD_DEVIATION 0.09 • n=14 Participants • Only measured on the participants who received study medication
Partial Thromboplastin Time (PTT)
27.16 sec
STANDARD_DEVIATION 2.48 • n=14 Participants • Only measured on the participants who received study medication

PRIMARY outcome

Timeframe: Baseline, 4 weeks

Population: Data reported only for those participants who completed both interventions.

Assay performed for soluble VCAM-1 using a commercially available enzyme-linked immunosorbent assay (ELISA).

Outcome measures

Outcome measures
Measure
Rivaroxaban
n=13 Participants
Participants who received Rivaroxaban 20 mg tablet in either the first or the second half of the study
Placebo
n=13 Participants
Participants who received placebo tablet (matching Rivaroxaban 20 mg) in either the first or the second half of the study
Change From Baseline to 4 Weeks in Soluble Vascular Cell Adhesion Molecule-1 (VCAM-1)
40.9 pg/mL
Interval -115.5 to 197.2
10.7 pg/mL
Interval -84.5 to 105.8

PRIMARY outcome

Timeframe: Baseline, 4 weeks

Population: Data reported only for those participants who completed both interventions.

Assay performed for IL-6 using a commercially available enzyme-linked immunosorbent assay (ELISA).

Outcome measures

Outcome measures
Measure
Rivaroxaban
n=13 Participants
Participants who received Rivaroxaban 20 mg tablet in either the first or the second half of the study
Placebo
n=13 Participants
Participants who received placebo tablet (matching Rivaroxaban 20 mg) in either the first or the second half of the study
Change From Baseline to 4 Weeks in Interleukin-6 (IL-6)
-1.1 pg/mL
Interval -4.47 to 2.28
-0.54 pg/mL
Interval -1.69 to 0.62

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: 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.

Interleukin-2 (IL-2) was measured using Luminex MAP technology at the UNC core facility

Outcome measures

Outcome measures
Measure
Rivaroxaban
n=7 Participants
Participants who received Rivaroxaban 20 mg tablet in either the first or the second half of the study
Placebo
n=7 Participants
Participants who received placebo tablet (matching Rivaroxaban 20 mg) in either the first or the second half of the study
Change From Baseline to Week 4 in the Plasma Marker of Inflammation IL-2
-1.14 pg/mL
Interval -4.13 to 1.85
0.36 pg/mL
Interval -3.48 to 4.2

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: 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.

Interleukin-8 (IL-8) was measured using Luminex MAP technology at the UNC core facility

Outcome measures

Outcome measures
Measure
Rivaroxaban
n=9 Participants
Participants who received Rivaroxaban 20 mg tablet in either the first or the second half of the study
Placebo
n=8 Participants
Participants who received placebo tablet (matching Rivaroxaban 20 mg) in either the first or the second half of the study
Change From Baseline to Week 4 in the Plasma Marker of Inflammation IL-8
0.95 pg/mL
Interval -41.83 to 43.72
-4.08 pg/mL
Interval -38.36 to 30.19

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: 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.

high sensitivity C-reactive protein (hsCRP) was measured using Luminex MAP technology at the UNC core facility.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: 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.

myeloperoxidase (MPO) was measured using Luminex MAP technology at the UNC core facility.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: 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.

tumor necrosis factor alpha (TNF-a) was measured using Luminex MAP technology at the UNC core facility.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: 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.

secretory phospholipase A2 (sPLA2) was measured using Luminex MAP technology at the UNC core facility

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: 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.

levels of soluble intracellular adhesion molecule (sICAM) were measured using a commercially available ELISA

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: All participants randomized to each treatment were analyzed.

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)

Outcome measures

Outcome measures
Measure
Rivaroxaban
n=14 Participants
Participants who received Rivaroxaban 20 mg tablet in either the first or the second half of the study
Placebo
n=13 Participants
Participants who received placebo tablet (matching Rivaroxaban 20 mg) in either the first or the second half of the study
Change From Baseline to Week 4 in TH1
0.84 seconds
Interval -0.79 to 2.47
-0.51 seconds
Interval -2.72 to 1.7

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: All participants randomized to each treatment were analyzed.

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)

Outcome measures

Outcome measures
Measure
Rivaroxaban
n=14 Participants
Participants who received Rivaroxaban 20 mg tablet in either the first or the second half of the study
Placebo
n=13 Participants
Participants who received placebo tablet (matching Rivaroxaban 20 mg) in either the first or the second half of the study
Change From Baseline to Week 4 in TM
-0.97 seconds
Interval -5.71 to 3.77
-2.01 seconds
Interval -6.82 to 2.81

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: All participants randomized to each treatment were analyzed.

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)

Outcome measures

Outcome measures
Measure
Rivaroxaban
n=14 Participants
Participants who received Rivaroxaban 20 mg tablet in either the first or the second half of the study
Placebo
n=13 Participants
Participants who received placebo tablet (matching Rivaroxaban 20 mg) in either the first or the second half of the study
Change From Baseline to Week 4 in AH
128 perfusion units*seconds
Interval -373.0 to 628.0
-1189 perfusion units*seconds
Interval -2597.0 to 218.0

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: All participants randomized to each treatment were analyzed.

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)

Outcome measures

Outcome measures
Measure
Rivaroxaban
n=14 Participants
Participants who received Rivaroxaban 20 mg tablet in either the first or the second half of the study
Placebo
n=13 Participants
Participants who received placebo tablet (matching Rivaroxaban 20 mg) in either the first or the second half of the study
Change in Ratio From Baseline to Week 4 in AH/AO
0.05 ratio of AH to AO
Interval -0.46 to 0.57
-0.81 ratio of AH to AO
Interval -2.05 to 0.42

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: All participants randomized to each treatment were analyzed.

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)

Outcome measures

Outcome measures
Measure
Rivaroxaban
n=14 Participants
Participants who received Rivaroxaban 20 mg tablet in either the first or the second half of the study
Placebo
n=13 Participants
Participants who received placebo tablet (matching Rivaroxaban 20 mg) in either the first or the second half of the study
Change From Baseline to Week 4 in PF
3.14 perfusion units
Interval -9.08 to 15.36
-12.62 perfusion units
Interval -26.63 to 1.4

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: All participants randomized to each treatment were analyzed.

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)

Outcome measures

Outcome measures
Measure
Rivaroxaban
n=14 Participants
Participants who received Rivaroxaban 20 mg tablet in either the first or the second half of the study
Placebo
n=13 Participants
Participants who received placebo tablet (matching Rivaroxaban 20 mg) in either the first or the second half of the study
Change From Baseline to Week 4 in RF
0.29 perfusion units
Interval -1.47 to 2.05
-0.62 perfusion units
Interval -2.96 to 1.73

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: Data reported only for those participants who completed both interventions.

Assay for thrombin antithrombin (TAT) complexes performed using commercially available enzyme-linked immunosorbent assay (ELISA).

Outcome measures

Outcome measures
Measure
Rivaroxaban
n=13 Participants
Participants who received Rivaroxaban 20 mg tablet in either the first or the second half of the study
Placebo
n=13 Participants
Participants who received placebo tablet (matching Rivaroxaban 20 mg) in either the first or the second half of the study
Change From Baseline to Week 4 in TAT
-34.44 ug/mL
Interval -69.4 to 0.53
0.35 ug/mL
Interval -3.77 to 4.47

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: Data reported only for those participants who completed both interventions.

Assay for D--dimer is performed using commercially available enzyme-linked immunosorbent assay (ELISA).

Outcome measures

Outcome measures
Measure
Rivaroxaban
n=13 Participants
Participants who received Rivaroxaban 20 mg tablet in either the first or the second half of the study
Placebo
n=13 Participants
Participants who received placebo tablet (matching Rivaroxaban 20 mg) in either the first or the second half of the study
Change From Baseline to Week 4 in D-Dimer
-471 ng/mL
Interval -1654.0 to 712.0
-1035 ng/mL
Interval -3880.0 to 1810.0

Adverse Events

Rivaroxaban

Serious events: 1 serious events
Other events: 8 other events
Deaths: 0 deaths

Placebo

Serious events: 1 serious events
Other events: 7 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Rivaroxaban
n=14 participants at risk
Participants who received Rivaroxaban 20 mg tablet in either the first or the second half of the study
Placebo
n=13 participants at risk
Participants who received placebo tablet (matching Rivaroxaban 20 mg) in either the first or the second half of the study
Blood and lymphatic system disorders
painful crisis with bacteremia
0.00%
0/14 • Data collected from date of informed consent to end of study visit, approximately 3 months
The safety analysis population includes all participants exposed to any study intervention evaluated in this study.
7.7%
1/13 • Number of events 1 • Data collected from date of informed consent to end of study visit, approximately 3 months
The safety analysis population includes all participants exposed to any study intervention evaluated in this study.
Respiratory, thoracic and mediastinal disorders
pneumonia
7.1%
1/14 • Number of events 1 • Data collected from date of informed consent to end of study visit, approximately 3 months
The safety analysis population includes all participants exposed to any study intervention evaluated in this study.
0.00%
0/13 • Data collected from date of informed consent to end of study visit, approximately 3 months
The safety analysis population includes all participants exposed to any study intervention evaluated in this study.

Other adverse events

Other adverse events
Measure
Rivaroxaban
n=14 participants at risk
Participants who received Rivaroxaban 20 mg tablet in either the first or the second half of the study
Placebo
n=13 participants at risk
Participants who received placebo tablet (matching Rivaroxaban 20 mg) in either the first or the second half of the study
Vascular disorders
pain crisis treated at home
28.6%
4/14 • Number of events 6 • Data collected from date of informed consent to end of study visit, approximately 3 months
The safety analysis population includes all participants exposed to any study intervention evaluated in this study.
15.4%
2/13 • Number of events 2 • Data collected from date of informed consent to end of study visit, approximately 3 months
The safety analysis population includes all participants exposed to any study intervention evaluated in this study.
General disorders
headache
14.3%
2/14 • Number of events 2 • Data collected from date of informed consent to end of study visit, approximately 3 months
The safety analysis population includes all participants exposed to any study intervention evaluated in this study.
7.7%
1/13 • Number of events 1 • Data collected from date of informed consent to end of study visit, approximately 3 months
The safety analysis population includes all participants exposed to any study intervention evaluated in this study.
General disorders
chest pain
21.4%
3/14 • Number of events 3 • Data collected from date of informed consent to end of study visit, approximately 3 months
The safety analysis population includes all participants exposed to any study intervention evaluated in this study.
0.00%
0/13 • Data collected from date of informed consent to end of study visit, approximately 3 months
The safety analysis population includes all participants exposed to any study intervention evaluated in this study.
Musculoskeletal and connective tissue disorders
back pain
7.1%
1/14 • Number of events 1 • Data collected from date of informed consent to end of study visit, approximately 3 months
The safety analysis population includes all participants exposed to any study intervention evaluated in this study.
7.7%
1/13 • Number of events 1 • Data collected from date of informed consent to end of study visit, approximately 3 months
The safety analysis population includes all participants exposed to any study intervention evaluated in this study.
Blood and lymphatic system disorders
neutropenia
7.1%
1/14 • Number of events 1 • Data collected from date of informed consent to end of study visit, approximately 3 months
The safety analysis population includes all participants exposed to any study intervention evaluated in this study.
15.4%
2/13 • Number of events 3 • Data collected from date of informed consent to end of study visit, approximately 3 months
The safety analysis population includes all participants exposed to any study intervention evaluated in this study.
Skin and subcutaneous tissue disorders
ankle laceration
0.00%
0/14 • Data collected from date of informed consent to end of study visit, approximately 3 months
The safety analysis population includes all participants exposed to any study intervention evaluated in this study.
7.7%
1/13 • Number of events 1 • Data collected from date of informed consent to end of study visit, approximately 3 months
The safety analysis population includes all participants exposed to any study intervention evaluated in this study.
Skin and subcutaneous tissue disorders
tick bite
7.1%
1/14 • Number of events 1 • Data collected from date of informed consent to end of study visit, approximately 3 months
The safety analysis population includes all participants exposed to any study intervention evaluated in this study.
0.00%
0/13 • Data collected from date of informed consent to end of study visit, approximately 3 months
The safety analysis population includes all participants exposed to any study intervention evaluated in this study.
Gastrointestinal disorders
diarrhea, nausea and vomiting
14.3%
2/14 • Number of events 3 • Data collected from date of informed consent to end of study visit, approximately 3 months
The safety analysis population includes all participants exposed to any study intervention evaluated in this study.
0.00%
0/13 • Data collected from date of informed consent to end of study visit, approximately 3 months
The safety analysis population includes all participants exposed to any study intervention evaluated in this study.
General disorders
insomnia
7.1%
1/14 • Number of events 1 • Data collected from date of informed consent to end of study visit, approximately 3 months
The safety analysis population includes all participants exposed to any study intervention evaluated in this study.
0.00%
0/13 • Data collected from date of informed consent to end of study visit, approximately 3 months
The safety analysis population includes all participants exposed to any study intervention evaluated in this study.
Skin and subcutaneous tissue disorders
tinea versicolor
7.1%
1/14 • Number of events 1 • Data collected from date of informed consent to end of study visit, approximately 3 months
The safety analysis population includes all participants exposed to any study intervention evaluated in this study.
0.00%
0/13 • Data collected from date of informed consent to end of study visit, approximately 3 months
The safety analysis population includes all participants exposed to any study intervention evaluated in this study.
Gastrointestinal disorders
elevate liver enzymes
0.00%
0/14 • Data collected from date of informed consent to end of study visit, approximately 3 months
The safety analysis population includes all participants exposed to any study intervention evaluated in this study.
7.7%
1/13 • Number of events 1 • Data collected from date of informed consent to end of study visit, approximately 3 months
The safety analysis population includes all participants exposed to any study intervention evaluated in this study.
Respiratory, thoracic and mediastinal disorders
cough, fever, body aches, congestion
7.1%
1/14 • Number of events 1 • Data collected from date of informed consent to end of study visit, approximately 3 months
The safety analysis population includes all participants exposed to any study intervention evaluated in this study.
15.4%
2/13 • Number of events 2 • Data collected from date of informed consent to end of study visit, approximately 3 months
The safety analysis population includes all participants exposed to any study intervention evaluated in this study.
Musculoskeletal and connective tissue disorders
pain in lower extremities
7.1%
1/14 • Number of events 1 • Data collected from date of informed consent to end of study visit, approximately 3 months
The safety analysis population includes all participants exposed to any study intervention evaluated in this study.
7.7%
1/13 • Number of events 1 • Data collected from date of informed consent to end of study visit, approximately 3 months
The safety analysis population includes all participants exposed to any study intervention evaluated in this study.
General disorders
dyspnea
7.1%
1/14 • Number of events 1 • Data collected from date of informed consent to end of study visit, approximately 3 months
The safety analysis population includes all participants exposed to any study intervention evaluated in this study.
0.00%
0/13 • Data collected from date of informed consent to end of study visit, approximately 3 months
The safety analysis population includes all participants exposed to any study intervention evaluated in this study.
Renal and urinary disorders
pelvic pressure with urination
7.1%
1/14 • Number of events 1 • Data collected from date of informed consent to end of study visit, approximately 3 months
The safety analysis population includes all participants exposed to any study intervention evaluated in this study.
0.00%
0/13 • Data collected from date of informed consent to end of study visit, approximately 3 months
The safety analysis population includes all participants exposed to any study intervention evaluated in this study.
General disorders
right flank pain
7.1%
1/14 • Number of events 1 • Data collected from date of informed consent to end of study visit, approximately 3 months
The safety analysis population includes all participants exposed to any study intervention evaluated in this study.
0.00%
0/13 • Data collected from date of informed consent to end of study visit, approximately 3 months
The safety analysis population includes all participants exposed to any study intervention evaluated in this study.

Additional Information

Dr. Kenneth Ataga

University of Tennessee Center for the Heath Sciences

Phone: 901.448.3181

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place