Trial Outcomes & Findings for Microvascular Blood Flow in Sickle Cell Anemia (NCT NCT01566890)

Last Updated: 2024-06-26

Results Overview

Primary outcome measure will be a 40% increase in skeletal muscle microvascular blood flow when 24 hour measurements are compared to baseline in subjects receiving Regadenoson. We took measurements in patients who received Regadenoson, as well as Sickle Cell controls. Both arms had microvascular blood flow (volume x velocity) measured at baseline and 24-hours, and those values were compared. A change ratio of \>1 means that the flow rate increased at 24 hours and a change ratio of \<1 means that the flow rate decreased at 24 hours.

Recruitment status

COMPLETED

Study phase

Target enrollment

91 participants

Primary outcome timeframe

Between baseline and 24 hours

Results posted on

2024-06-26

Participant Flow

Participant milestones

Participant milestones
Measure	Regadenoson ARM Adult subjects with sickle cell anemia will receive a regadenoson infusion with contrast-enhanced ultrasound regadenoson infusion with contrast-enhanced ultrasound: Subjects who are not having a pain crisis receive a 24-hour infusion of regadenoson. Contrast-enhanced ultrasound will be performed four times during the 24 hour regadenoson infusion	Sickle Cell Controls ARM Adult subjects with sickle cell anemia will receive contrast-enhanced ultrasound contrast-enhanced ultrasound: Subjects who are not having a pain crisis will have contrast-enhanced ultrasound performed up to four times over a two-day period. Time points will resemble the time course used for the Regadenoson Arm, although no investigational drug will be given.	Sickle Cell Crisis ARM Adult subjects who had a sickle cell crisis Adults subjects with sickle cell anemia will receive contrast-enhanced ultrasound contrast-enhanced ultrasound: Contrast-enhanced ultrasound will be performed on adults with sickle cell anemia at baseline who are not having a pain crisis and performed again during a pain crisis	Healthy Controls Healthy African American control subjects without sickle cell anemia will receive contrast-enhanced ultrasound	Technique Optimization Controls Healthy volunteers will undergo contrast-enhanced ultrasound.
Overall Study STARTED	32	10	21	21	7
Overall Study COMPLETED	21	6	10	7	0
Overall Study NOT COMPLETED	11	4	11	14	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Regadenoson ARM Adult subjects with sickle cell anemia will receive a regadenoson infusion with contrast-enhanced ultrasound regadenoson infusion with contrast-enhanced ultrasound: Subjects who are not having a pain crisis receive a 24-hour infusion of regadenoson. Contrast-enhanced ultrasound will be performed four times during the 24 hour regadenoson infusion	Sickle Cell Controls ARM Adult subjects with sickle cell anemia will receive contrast-enhanced ultrasound contrast-enhanced ultrasound: Subjects who are not having a pain crisis will have contrast-enhanced ultrasound performed up to four times over a two-day period. Time points will resemble the time course used for the Regadenoson Arm, although no investigational drug will be given.	Sickle Cell Crisis ARM Adult subjects who had a sickle cell crisis Adults subjects with sickle cell anemia will receive contrast-enhanced ultrasound contrast-enhanced ultrasound: Contrast-enhanced ultrasound will be performed on adults with sickle cell anemia at baseline who are not having a pain crisis and performed again during a pain crisis	Healthy Controls Healthy African American control subjects without sickle cell anemia will receive contrast-enhanced ultrasound	Technique Optimization Controls Healthy volunteers will undergo contrast-enhanced ultrasound.
Overall Study Adverse Event	1	0	0	0	0
Overall Study Withdrawal by Subject	3	1	1	1	0
Overall Study Screen failure	6	0	1	1	0
Overall Study Incomplete CEU data	1	3	5	8	0
Overall Study Lost to Follow-up	0	0	4	4	0
Overall Study Other	0	0	0	0	7

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Regadenoson ARM n=20 Participants Adult subjects with sickle cell anemia will receive a regadenoson infusion with contrast-enhanced ultrasound regadenoson infusion with contrast-enhanced ultrasound: Subjects who are not having a pain crisis receive a 24-hour infusion of regadenoson. Contrast-enhanced ultrasound will be performed four times during the 24 hour regadenoson infusion	Sickle Cell Controls ARM n=6 Participants Adult subjects with sickle cell anemia will receive contrast-enhanced ultrasound contrast-enhanced ultrasound: Subjects who are not having a pain crisis will have contrast-enhanced ultrasound performed up to four times over a two-day period. Time points will resemble the time course used for the Regadenoson Arm, although no investigational drug will be given.	Sickle Cell Crisis ARM n=6 Participants Adult subjects who had a sickle cell crisis Adults subjects with sickle cell anemia will receive contrast-enhanced ultrasound contrast-enhanced ultrasound: Contrast-enhanced ultrasound will be performed on adults with sickle cell anemia at baseline who are not having a pain crisis and performed again during a pain crisis	Healthy Controls n=7 Participants Healthy African American control subjects without sickle cell anemia will receive contrast-enhanced ultrasound. They were not included in the analysis due to the number of participants who did not complete the study (therefore no meaningful ultrasounds to interpret).	Technique Optimization Controls Healthy volunteers will undergo contrast-enhanced ultrasound. There was no data collected for this arm.	Total n=39 Participants Total of all reporting groups
Age, Continuous	25 years n=20 Participants	35 years n=6 Participants	26 years n=6 Participants	26 years n=7 Participants	—	26 years n=39 Participants
Sex: Female, Male Female	0 Participants n=20 Participants	0 Participants n=6 Participants	0 Participants n=6 Participants	7 Participants n=7 Participants	—	7 Participants n=39 Participants
Sex: Female, Male Male	20 Participants n=20 Participants	6 Participants n=6 Participants	6 Participants n=6 Participants	0 Participants n=7 Participants	—	32 Participants n=39 Participants
Race and Ethnicity Not Collected	—	—	—	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment United States	20 participants n=20 Participants	6 participants n=6 Participants	6 participants n=6 Participants	7 participants n=7 Participants	—	39 participants n=39 Participants

PRIMARY outcome

Timeframe: Between baseline and 24 hours

Population: There were 20 participants in the Regadenoson arm, and 6 participants acted as sickle cell controls. Sickle Cell Crisis ARM is not included because arm was not measured by CEUS in a similar timeframe as Regadenoson ARM and Sickle Cell Controls ARM, as indicated in Results Baseline Characteristics Arm/Group Description for Sickle Cell Crisis ARM.

Outcome measures

Outcome measures
Measure	Regadenoson ARM n=20 Participants Adult subjects with sickle cell anemia will receive a regadenoson infusion with contrast-enhanced ultrasound regadenoson infusion with contrast-enhanced ultrasound: Subjects who are not having a pain crisis receive a 24-hour infusion of regadenoson. Contrast-enhanced ultrasound will be performed four times during the 24 hour regadenoson infusion	Sickle Cell Controls ARM n=6 Participants Adult subjects with sickle cell anemia will receive contrast-enhanced ultrasound contrast-enhanced ultrasound: Subjects who are not having a pain crisis will have contrast-enhanced ultrasound performed up to four times over a two-day period. Time points will resemble the time course used for the Regadenoson Arm, although no investigational drug will be given.
Microvascular Blood Flow Rate Change	1.09 Ratio of change Interval 0.39 to 4.12	0.86 Ratio of change Interval 0.24 to 2.82

SECONDARY outcome

Timeframe: Between baseline and between 7-30 days after pain crisis, if feasible

We planned to examine differences in microvascular blood flow using contrast-enhanced ultrasound (CEU) in adults with sickle cell anemia age 18 and older at baseline state compared to a pain crisis. We were measuring changes in microvascular blood flow in subjects with sickle cell anemia during a pain crisis by examining differences in microvascular blood flow using contrast-enhanced ultrasound at a baseline state, and comparing those measurements to contrast-enhanced ultrasound measurements during a pain crisis. A change ratio of \>1 means that the flow rate increased during a pain crisis and a change ratio of \<1 means that the flow rate decreased during a pain crisis.

Outcome measures

Outcome measures
Measure	Regadenoson ARM n=6 Participants Adult subjects with sickle cell anemia will receive a regadenoson infusion with contrast-enhanced ultrasound regadenoson infusion with contrast-enhanced ultrasound: Subjects who are not having a pain crisis receive a 24-hour infusion of regadenoson. Contrast-enhanced ultrasound will be performed four times during the 24 hour regadenoson infusion	Sickle Cell Controls ARM Adult subjects with sickle cell anemia will receive contrast-enhanced ultrasound contrast-enhanced ultrasound: Subjects who are not having a pain crisis will have contrast-enhanced ultrasound performed up to four times over a two-day period. Time points will resemble the time course used for the Regadenoson Arm, although no investigational drug will be given.
MVBF Ratio of Change During a Pain Crisis	0.65 Ratio of change Interval 0.6 to 0.95	—

SECONDARY outcome

Timeframe: 5 years

Population: African American controls subjects were enrolled. The ultrasounds were not able to be examined and therefore no data generated to provide.

Examine microvascular blood flow using contrast-enhanced ultrasounds in adult subjects with sickle cell anemia compared to microvascular blood flow of healthy African-American adults

Outcome measures

Outcome data not reported

Adverse Events

Regadenoson ARM

Serious events: 5 serious events

Other events: 16 other events

Deaths: 0 deaths

Sickle Cell Controls ARM

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Sickle Cell CEU ARM

Serious events: 3 serious events

Other events: 4 other events

Deaths: 0 deaths

Healthy Control ARM

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Technique Optimization Controls

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Regadenoson ARM n=32 participants at risk Adult subjects with sickle cell anemia will receive a regadenoson infusion with contrast-enhanced ultrasound regadenoson infusion with contrast-enhanced ultrasound: Subjects who are not having a pain crisis receive a 24-hour infusion of regadenoson. Contrast-enhanced ultrasound will be performed four times during the 24 hour regadenoson infusion	Sickle Cell Controls ARM n=10 participants at risk Adult subjects with sickle cell anemia will receive contrast-enhanced ultrasound contrast-enhanced ultrasound: Subjects who are not having a pain crisis will have contrast-enhanced ultrasound performed up to four times over a two-day period. Time points will resemble the time course used for the Regadenoson Arm, although no investigational drug will be given.	Sickle Cell CEU ARM n=21 participants at risk Adults subjects with sickle cell anemia will receive contrast-enhanced ultrasound contrast-enhanced ultrasound: Contrast-enhanced ultrasound will be performed on adults with sickle cell anemia at baseline who are not having a pain crisis and performed again during a pain crisis	Healthy Control ARM n=21 participants at risk Healthy African American control subjects without sickle cell anemia will receive contrast-enhanced ultrasound contrast-enhanced ultrasound: Contrast-enhanced ultrasound will be performed on healthy control subjects at baseline, on the first day of the study and 30 days later	Technique Optimization Controls n=7 participants at risk Healthy volunteers will undergo contrast-enhanced ultrasound. contrast-enhanced ultrasound: Contrast-enhanced ultrasound will be performed on healthy volunteers (Technique Optimization Controls)
Vascular disorders Vaso Occlusive Crisis	12.5% 4/32 • Number of events 4 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	0.00% 0/10 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	0.00% 0/21 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	0.00% 0/21 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	0.00% 0/7 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.
Vascular disorders Severe Pain	3.1% 1/32 • Number of events 1 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	0.00% 0/10 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	14.3% 3/21 • Number of events 3 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	0.00% 0/21 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	0.00% 0/7 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.

Other adverse events

Other adverse events
Measure	Regadenoson ARM n=32 participants at risk Adult subjects with sickle cell anemia will receive a regadenoson infusion with contrast-enhanced ultrasound regadenoson infusion with contrast-enhanced ultrasound: Subjects who are not having a pain crisis receive a 24-hour infusion of regadenoson. Contrast-enhanced ultrasound will be performed four times during the 24 hour regadenoson infusion	Sickle Cell Controls ARM n=10 participants at risk Adult subjects with sickle cell anemia will receive contrast-enhanced ultrasound contrast-enhanced ultrasound: Subjects who are not having a pain crisis will have contrast-enhanced ultrasound performed up to four times over a two-day period. Time points will resemble the time course used for the Regadenoson Arm, although no investigational drug will be given.	Sickle Cell CEU ARM n=21 participants at risk Adults subjects with sickle cell anemia will receive contrast-enhanced ultrasound contrast-enhanced ultrasound: Contrast-enhanced ultrasound will be performed on adults with sickle cell anemia at baseline who are not having a pain crisis and performed again during a pain crisis	Healthy Control ARM n=21 participants at risk Healthy African American control subjects without sickle cell anemia will receive contrast-enhanced ultrasound contrast-enhanced ultrasound: Contrast-enhanced ultrasound will be performed on healthy control subjects at baseline, on the first day of the study and 30 days later	Technique Optimization Controls n=7 participants at risk Healthy volunteers will undergo contrast-enhanced ultrasound. contrast-enhanced ultrasound: Contrast-enhanced ultrasound will be performed on healthy volunteers (Technique Optimization Controls)
General disorders Pain	40.6% 13/32 • Number of events 17 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	10.0% 1/10 • Number of events 1 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	14.3% 3/21 • Number of events 3 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	0.00% 0/21 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	0.00% 0/7 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.
Gastrointestinal disorders Nausea and/or Vomiting	9.4% 3/32 • Number of events 5 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	0.00% 0/10 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	0.00% 0/21 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	0.00% 0/21 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	0.00% 0/7 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.
Respiratory, thoracic and mediastinal disorders Cough	9.4% 3/32 • Number of events 5 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	0.00% 0/10 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	0.00% 0/21 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	0.00% 0/21 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	0.00% 0/7 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.
Musculoskeletal and connective tissue disorders Arthralgia	9.4% 3/32 • Number of events 3 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	0.00% 0/10 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	0.00% 0/21 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	0.00% 0/21 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	0.00% 0/7 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.
Skin and subcutaneous tissue disorders Cheilitis	0.00% 0/32 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	0.00% 0/10 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	4.8% 1/21 • Number of events 1 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	0.00% 0/21 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	0.00% 0/7 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.
Nervous system disorders Dysguesia	0.00% 0/32 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	0.00% 0/10 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	0.00% 0/21 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	4.8% 1/21 • Number of events 2 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	0.00% 0/7 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.
Eye disorders Blurred Vision	0.00% 0/32 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	0.00% 0/10 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	4.8% 1/21 • Number of events 1 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	0.00% 0/21 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	0.00% 0/7 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.
Cardiac disorders Hypotension	0.00% 0/32 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	10.0% 1/10 • Number of events 1 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	0.00% 0/21 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	0.00% 0/21 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	0.00% 0/7 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.
Blood and lymphatic system disorders Hot flash	0.00% 0/32 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	10.0% 1/10 • Number of events 1 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	0.00% 0/21 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	0.00% 0/21 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.	0.00% 0/7 • Adverse events were monitored from the time participants signed consent until they completed their last study visit (about 30 days). The definition of an adverse event did not differ from the clinicaltrials.gov definition.

Additional Information

Joshua Field, MD

Medical College of Wisconsin Department of Hematology

Phone: 414-937-6896

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place