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

This study has been completed.
Sponsor:
Collaborator:
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
No text entered.

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  
Number of Participants  
[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┬ácells/L]
Mean (Standard Deviation)
  0.046  (0.091)     0.058  (0.096)     0.052  (0.094)  
Zubrod score [2]
[units: participants]
     
0 to 2     19     18     37  
3 to 5     39     38     77  
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  
[1]

ANC = Absolute neutrophil count.

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

[2] 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.



  Outcome Measures
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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


No publications provided


Responsible Party: New England Research Institutes
ClinicalTrials.gov Identifier: NCT00627393     History of Changes
Other Study ID Numbers: 557, U01HL072268, 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