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Safety and Effectiveness of Granulocyte Transfusions in Resolving Infection in People With Neutropenia (The RING Study) (RING)

This study has been completed.
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
New England Research Institutes
ClinicalTrials.gov Identifier:
NCT00627393
First received: February 28, 2008
Last updated: April 16, 2015
Last verified: April 2014
Results First Received: December 2, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Single Blind (Outcomes Assessor);   Primary Purpose: Treatment
Conditions: Neutropenia
Infection
Interventions: Drug: Standard antimicrobial therapy
Biological: Granulocyte transfusions
Drug: G-CSF/dexamethasone
Device: Apheresis machine

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Control Arm Received antimicrobial therapy alone.
Granulocyte Arm Received G-CSF/dexamethasone-mobilized granulocyte transfusions in addition to antimicrobial therapy.

Participant Flow for 2 periods

Period 1:   Intention-To-Treat Analysis
    Control Arm   Granulocyte Arm
STARTED   58   56 
COMPLETED   49   48 
NOT COMPLETED   9   8 
Adjudication indeterminate                5                3 
Withdrawal by patient/family/physician                4                5 

Period 2:   Per-Protocol Analysis
    Control Arm   Granulocyte Arm
STARTED   49   48 
COMPLETED   39   35 
NOT COMPLETED   10   13 
Received unstimulated/no granulocytes                6                3 
Withdrawal by patient/family/physician                4                10 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized subjects.

Reporting Groups
  Description
Control Arm Received antimicrobial therapy alone.
Granulocyte Arm Received G-CSF/dexamethasone-mobilized granulocyte transfusions in addition to antimicrobial therapy.
Total Total of all reporting groups

Baseline Measures
   Control Arm   Granulocyte Arm   Total 
Overall Participants Analyzed 
[Units: Participants]
 58   56   114 
Age 
[Units: Participants]
     
<=18 years   6   4   10 
Between 18 and 65 years   39   32   71 
>=65 years   13   20   33 
Age 
[Units: Years]
Mean (Standard Deviation)
 49.1  (19.8)   54.8  (16.3)   51.9  (18.3) 
Gender 
[Units: Participants]
     
Female   28   23   51 
Male   30   33   63 
Ethnicity (NIH/OMB) 
[Units: Participants]
     
Hispanic or Latino   5   1   6 
Not Hispanic or Latino   40   44   84 
Unknown or Not Reported   13   11   24 
Race (NIH/OMB) 
[Units: Participants]
     
American Indian or Alaska Native   0   0   0 
Asian   4   1   5 
Native Hawaiian or Other Pacific Islander   0   0   0 
Black or African American   1   6   7 
White   39   40   79 
More than one race   1   0   1 
Unknown or Not Reported   13   9   22 
Weight 
[Units: Kg]
Mean (Standard Deviation)
 76.0  (23.8)   78.7  (20.6)   77.3  (22.2) 
Cause of neutropenia 
[Units: Participants]
     
Chemotherapy only   43   44   87 
Infection   7   3   10 
HST (or preparation for HST)   8   9   17 
ANC prior to randomization [1] 
[Units: X10^9 cells/L]
Mean (Standard Deviation)
 0.046  (0.091)   0.058  (0.096)   0.052  (0.094) 
[1]

ANC = Absolute neutrophil count.

Subjects with ANC less than 500/mm^3 were considered to have severe neutropenia.

Zubrod score [1] 
[Units: Participants]
     
0 to 2   19   18   37 
3 to 5   39   38   77 
[1] The Zubrod scoring system ranks patients on their functionality on a scale from 0-5. Zubrod score category "0 to 2" represents asymptomatic, symptomatic but completely ambulatory, or symptomatic and 50% in bed during the day. Zubrod score category "3 to 5" represents symptomatic and more than 50% in bed (but not bedbound), being bedbound or completely disabled, or being moribund.
Infection type 
[Units: Participants]
     
Bacteremia only   16   17   33 
Tissue bacterial infection   15   13   28 
Fungemia only   8   5   13 
Tissue fungal infection   19   21   40 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percentage of Participants Who Are Alive at 42 Days After Treatment and Have Had Microbial Response   [ Time Frame: Measured at Day 42 ]

2.  Secondary:   Serious Granulocyte Transfusion Reactions, Including Febrile, Allergic, and Pulmonary Reactions (Transfusion Arm Only)   [ Time Frame: Measured within 6 hours after end of transfusion ]

3.  Secondary:   Graft Versus Host Disease Among Recipients of Allogeneic Stem Cell Transplantation   [ Time Frame: Measured at Day 42 ]

4.  Secondary:   Overall Incidence of Adverse Effects   [ Time Frame: Measured through Day 42 ]

5.  Secondary:   Fever Resolution   [ Time Frame: Measured through Day 42 ]

6.  Secondary:   Long-term Survival   [ Time Frame: Measured at Month 3 ]

7.  Secondary:   Serious Adverse Events in Granulocyte Donors   [ Time Frame: Measured at Week 1 after G-CSF administration ]

8.  Secondary:   Donor Availability (Proportion of Scheduled Granulocyte Transfusion Days on Which Granulocytes Were Available)   [ Time Frame: Measured through study completion ]

9.  Secondary:   Evaluation of Granulocyte Yield   [ Time Frame: Measured immediately after each granulocyte donation ]

10.  Secondary:   Alloimmunization, Defined as the Appearance of Anti-human Leukocyte Antigen (HLA) or Antineutrophil Antibodies   [ Time Frame: Measured at Days 14 and 42 ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   Yes

11.  Secondary:   Time to Negative Test for Fungal Antigenemia (e.g., Galactomannan Antigenemia Among Participants With Invasive Aspergillosis)   [ Time Frame: Measured at Days 7, 14, and 42 ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

12.  Secondary:   Time to Negative Blood Culture for Participants With Positive Blood Culture at Baseline   [ Time Frame: Measured through Day 42 ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

13.  Secondary:   Discontinuation of Granulocyte Transfusions Due to Toxicity or Intolerance   [ Time Frame: Measured through Day 42 ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   Yes


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Susan Assmann, PhD
Organization: New England Research Institutes, Inc.
phone: 617-972-3048
e-mail: sassmann@neriscience.com


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

Responsible Party: New England Research Institutes
ClinicalTrials.gov Identifier: NCT00627393     History of Changes
Other Study ID Numbers: 557
U01HL072268 ( US NIH Grant/Contract Award Number )
HL072268
HL072291
HL072196
HL072248
HL072191
HL072305
HL072028
HL072072
HL072355
HL072283
HL072346
HL072331
HL072290
Study First Received: February 28, 2008
Results First Received: December 2, 2014
Last Updated: April 16, 2015
Health Authority: United States: Federal Government