Rejuvesol® Washed RBC in Sickle Cell Patients Requiring Frequent Transfusions

• Sponsor: Duke University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02731157
• Collaborator: (none)
• Enrollment: 4
• Locations: 2
• Arms: 2
• Actual Duration (Months): 13
• Patients Per Site: 2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The objective of this proposal is to test the feasibility of red blood cell (RBC) rejuvenation to chronic transfusion in sickle cell disease (SCD) and the potential benefit of RBC rejuvenation in this population to determine if a larger clinical trial powered to definitively characterize the benefits of rejuvenation is warranted.

This is a small pilot study is to see if restoring important energy molecules (ATP and 2,3,DPG) in stored red blood cells before they are transfused, with a rejuvenating solution (Rejuvesol), offers any advantages to individuals over standard blood transfusion. Subjects will receive either rejuvenated (R) or standard (S) RBCs with each transfusion for 6 transfusions (over approximately a 6-month period) in a pre-defined order to maximize detection of any signal.

Condition or Disease	Intervention/Treatment	Phase
Sickle Cell Disease	Drug: Rejuvesol; Procedure: Blood transfusion	Phase 4

Detailed Description

Blood transfusion is part of the standard care for individuals that have sickle cell disease. Often these transfusions become needed quite frequently. The purpose of the red blood cells in the blood is to deliver oxygen to the organs and tissues of the body. People with sickle cell disease have abnormal red blood cells. Stored blood undergoes some changes that may make it less effective in achieving this goal.

The purpose of this study is to see if restoring important energy molecules (ATP and 2,3,DPG) in stored red blood cells before they are transfused, with a rejuvenating solution (Rejuvesol), offers any advantages to individuals over standard blood transfusion. This is a Food and Drug Administration (FDA) approved process that is described by the American Association of Blood Banks for prolonging blood storage but not used for everyday transfusions. The investigators want to use this process to improve blood transfused to individuals who need frequent transfusions. Potential advantages include better delivery of oxygen by the transfused red blood cells and easier release of oxygen to the tissues. In addition the study will assess how using the rejuvenated blood affects the interval between transfusions. This means possibly that transfusions may not be needed as often.

Although Rejuvesol has been previously approved by the FDA, it is not routinely used to prepare standard blood transfusions to individuals who have sickle cell disease. Use of Rejuvesol in this study is considered investigational.

Study Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: Non-Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Other
• Official Title: Rejuvesol® Washed RBC in Sickle Cell Patients Requiring Frequent Transfusions
• Actual Study Start Date: Dec 1, 2016
• Actual Primary Completion Date: Dec 31, 2017
• Actual Study Completion Date: Dec 31, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Transfusion with rejuvenated red blood cells (RBCs) Subjects with sickle cell disease will receive RBCs treated with Rejuvesol®. Scheduled red cell exchanges performed with the last 4 units of the exchange having been incubated with Rejuvesol® solution. Only transfusions necessary for the treatment of the sickle cell disease will be given for the purpose of the study.	Drug: Rejuvesol; Procedure: Blood transfusion; Only transfusions necessary for the treatment of the sickle cell disease will be given for the purpose of the study.
Active Comparator: Transfusion with standard red blood cells Subjects with sickle cell disease will receive standard RBCs. Only transfusions necessary for the treatment of the sickle cell disease will be given for the purpose of the study.	Procedure: Blood transfusion; Only transfusions necessary for the treatment of the sickle cell disease will be given for the purpose of the study.

Outcome Measures

Primary Outcome Measures

1. Average Percent Hemoglobin (HbA) Decrement Per Day [6 months]

   The %HbA decrement is the current pre-treatment HbA - previous post treatment HbA in %. The average %HbA decrement per day was calculated using matched pairs.

Secondary Outcome Measures

1. Actual HbA Decrement (g/dl) With Indexing to Calculated Circulating Blood Volume [6 months]

2. Actual HbA Decrement (g/dl) Without Indexing to Calculated Circulating Blood Volume [6 months]

3. Change in RBC Microparticles (MP) Counts [6 months]

4. Change in RBC/RBC-MP-mediated Thrombin Generation [6 months]

5. Change in p50 Pre- and Post-transfusion [6 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Stable, compliant, chronically transfused sickle cell disease (SCD) patients

• Currently maintained crisis-free with repeated RBC therapy for at least 3 consecutive sessions

• ≥18 years old

• Have Hb SS disease

• Have the capacity to give informed consent

Exclusion Criteria:

• Baseline need for washed RBCs

• Pre-treatment SaO2 < 92%.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States
2	Duke Univeristy Medical Center	Durham	North Carolina	United States	27710

Sponsors and Collaborators

• Duke University

Investigators

• Principal Investigator: Ian J Welsby, BSc MBBS, Duke University
• Principal Investigator: Jay Raval, MD, University of North Carolina

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 26, 2017

More Information

Publications

None provided.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT02731157
• Other Study ID Numbers: Pro00069955
• First Posted: Apr 7, 2016
• Last Update Posted: Jan 25, 2019
• Last Verified: Dec 1, 2018

• Additional relevant MeSH terms: Anemia, Sickle Cell

Study Results

Participant Flow

Arm/Group Title	All Study Participants
Arm/Group Description	Each participant in this 4 subject pilot study acted as their own control. Red cell exchanges (RCEs) occurred approximately every month and, over a 6 month period, the sequence of exchanges for each patient was: SRRRSS, where S=standard and R=rejuvenated RCEs.
Period Title: First Standard RCE
STARTED	4
COMPLETED	4
NOT COMPLETED	0
Period Title: First Standard RCE
STARTED	4
COMPLETED	3
NOT COMPLETED	1
Period Title: First Standard RCE
STARTED	3
COMPLETED	3
NOT COMPLETED	0
Period Title: First Standard RCE
STARTED	3
COMPLETED	3
NOT COMPLETED	0
Period Title: First Standard RCE
STARTED	3
COMPLETED	3
NOT COMPLETED	0
Period Title: First Standard RCE
STARTED	3
COMPLETED	3
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	Each participant in this 4 subject pilot study acted as their own control. Red cell exchanges (RCEs) occurred approximately every month and, over a 6 month period, the sequence of exchanges for each patient was: SRRRSS, where S=standard and R=rejuvenated RCEs.
Overall Participants	4
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	4 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	4 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	4 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	4 100%
White	0 0%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	4 100%

Outcome Measures

1. Primary Outcome

Title	Average Percent Hemoglobin (HbA) Decrement Per Day
Description	The %HbA decrement is the current pre-treatment HbA - previous post treatment HbA in %. The average %HbA decrement per day was calculated using matched pairs.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Each participant acted as their own control with a sequence of rejuvenated and standard exchanges over 6 months. One subject ended further study participation after only 1 rejuvenated RBC exchange; limited data available.

Arm/Group Title	Transfusion With Rejuvenated Red Blood Cells (RBCs)	Transfusion With Standard Red Blood Cells
Arm/Group Description	Subjects with sickle cell disease will receive RBCs treated with Rejuvesol®. Scheduled red cell exchanges performed with the last 4 units of the exchange having been incubated with Rejuvesol® solution. Only transfusions necessary for the treatment of the sickle cell disease will be given for the purpose of the study. Rejuvesol Blood transfusion: Only transfusions necessary for the treatment of the sickle cell disease will be given for the purpose of the study.	Subjects with sickle cell disease will receive standard RBCs. Only transfusions necessary for the treatment of the sickle cell disease will be given for the purpose of the study. Blood transfusion: Only transfusions necessary for the treatment of the sickle cell disease will be given for the purpose of the study.
Measure Participants	4	4
Mean (Full Range) [%HbA per day]	0.629	0.659

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Transfusion With Rejuvenated Red Blood Cells (RBCs), Transfusion With Standard Red Blood Cells
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.95
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.65
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Actual HbA Decrement (g/dl) With Indexing to Calculated Circulating Blood Volume
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Data not collected.

Arm/Group Title	Transfusion With Rejuvenated Red Blood Cells (RBCs)	Transfusion With Standard Red Blood Cells
Arm/Group Description	Subjects with sickle cell disease will receive RBCs treated with Rejuvesol®. Scheduled red cell exchanges performed with the last 4 units of the exchange having been incubated with Rejuvesol® solution. Only transfusions necessary for the treatment of the sickle cell disease will be given for the purpose of the study. Rejuvesol Blood transfusion: Only transfusions necessary for the treatment of the sickle cell disease will be given for the purpose of the study.	Subjects with sickle cell disease will receive standard RBCs. Only transfusions necessary for the treatment of the sickle cell disease will be given for the purpose of the study. Blood transfusion: Only transfusions necessary for the treatment of the sickle cell disease will be given for the purpose of the study.
Measure Participants	0	0

3. Secondary Outcome

Title	Actual HbA Decrement (g/dl) Without Indexing to Calculated Circulating Blood Volume
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Data not collected.

Arm/Group Title	Transfusion With Rejuvenated Red Blood Cells (RBCs)	Transfusion With Standard Red Blood Cells
Arm/Group Description	Subjects with sickle cell disease will receive RBCs treated with Rejuvesol®. Scheduled red cell exchanges performed with the last 4 units of the exchange having been incubated with Rejuvesol® solution. Only transfusions necessary for the treatment of the sickle cell disease will be given for the purpose of the study. Rejuvesol Blood transfusion: Only transfusions necessary for the treatment of the sickle cell disease will be given for the purpose of the study.	Subjects with sickle cell disease will receive standard RBCs. Only transfusions necessary for the treatment of the sickle cell disease will be given for the purpose of the study. Blood transfusion: Only transfusions necessary for the treatment of the sickle cell disease will be given for the purpose of the study.
Measure Participants	0	0

4. Secondary Outcome

Title	Change in RBC Microparticles (MP) Counts
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Data not collected.

Arm/Group Title	Transfusion With Rejuvenated Red Blood Cells (RBCs)	Transfusion With Standard Red Blood Cells
Arm/Group Description	Subjects with sickle cell disease will receive RBCs treated with Rejuvesol®. Scheduled red cell exchanges performed with the last 4 units of the exchange having been incubated with Rejuvesol® solution. Only transfusions necessary for the treatment of the sickle cell disease will be given for the purpose of the study. Rejuvesol Blood transfusion: Only transfusions necessary for the treatment of the sickle cell disease will be given for the purpose of the study.	Subjects with sickle cell disease will receive standard RBCs. Only transfusions necessary for the treatment of the sickle cell disease will be given for the purpose of the study. Blood transfusion: Only transfusions necessary for the treatment of the sickle cell disease will be given for the purpose of the study.
Measure Participants	0	0

5. Secondary Outcome

Title	Change in RBC/RBC-MP-mediated Thrombin Generation
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Data not collected.

Arm/Group Title	Transfusion With Rejuvenated Red Blood Cells (RBCs)	Transfusion With Standard Red Blood Cells
Arm/Group Description	Subjects with sickle cell disease will receive RBCs treated with Rejuvesol®. Scheduled red cell exchanges performed with the last 4 units of the exchange having been incubated with Rejuvesol® solution. Only transfusions necessary for the treatment of the sickle cell disease will be given for the purpose of the study. Rejuvesol Blood transfusion: Only transfusions necessary for the treatment of the sickle cell disease will be given for the purpose of the study.	Subjects with sickle cell disease will receive standard RBCs. Only transfusions necessary for the treatment of the sickle cell disease will be given for the purpose of the study. Blood transfusion: Only transfusions necessary for the treatment of the sickle cell disease will be given for the purpose of the study.
Measure Participants	0	0

6. Secondary Outcome

Title	Change in p50 Pre- and Post-transfusion
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Data not collected.

Arm/Group Title	Transfusion With Rejuvenated Red Blood Cells (RBCs)	Transfusion With Standard Red Blood Cells
Arm/Group Description	Subjects with sickle cell disease will receive RBCs treated with Rejuvesol®. Scheduled red cell exchanges performed with the last 4 units of the exchange having been incubated with Rejuvesol® solution. Only transfusions necessary for the treatment of the sickle cell disease will be given for the purpose of the study. Rejuvesol Blood transfusion: Only transfusions necessary for the treatment of the sickle cell disease will be given for the purpose of the study.	Subjects with sickle cell disease will receive standard RBCs. Only transfusions necessary for the treatment of the sickle cell disease will be given for the purpose of the study. Blood transfusion: Only transfusions necessary for the treatment of the sickle cell disease will be given for the purpose of the study.
Measure Participants	0	0

Adverse Events

Time Frame	6 months
Arm/Group Title	Transfusion With Standard RBCs		Transfusion With Rejuvenated RBCs
Arm/Group Description	Each participant received three standard red cell exchanges.		Each participant received three rejuvenated red cell exchanges.
All Cause Mortality
	Transfusion With Standard RBCs		Transfusion With Rejuvenated RBCs
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/4 (0%)
Serious Adverse Events
	Transfusion With Standard RBCs		Transfusion With Rejuvenated RBCs
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	Transfusion With Standard RBCs		Transfusion With Rejuvenated RBCs
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/4 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.