Last updated on June 2017

Study of INTERCEPT Blood System for Red Blood Cells in Regions at Potential Risk for Zika Virus Transfusion-Transmitted Infections (RedeS)


Brief description of study

Stage A: To evaluate the safety and efficacy of the INTERCEPT Blood System for Red Blood Cells Pathogen Reduction Treatment (PRT) in comparison to conventional RBCs in adult patients who require RBC transfusion support. Stage B: To provide early access to the INTERCEPT pathogen reduction system for RBC in regions where a substantial proportion of the population has been infected or is at risk of infection by the Zika virus (ZIKV), and the risk of asymptomatic infection among qualified blood donors is recognized. Besides the reduction of risk of transfusion transmitted ZIKV, the intent of the study is also to reduce the risk of transfusion-transmitted infections (TTI) in general, including transfusion related sepsis and other emerging or concurrent endemic pathogens (e.g. Dengue and Chikungunya), and to reduce the risk of TA-GVHD. As part of this treatment use study, additional data will be provided on the safety of INTERCEPT-treated RBCs (IBS RBCs) supplied for routine clinical transfusion practice.

Detailed Study Description

Stage A Eligible patients will be randomized and transfused with study RBCs (Test or Control with 1:1 ratio) according to local practices for up to 28 days of transfusion support. Following the 28-day transfusion support period, patients will be transfused with conventional RBC components as indicated by their treating physician. Patients will attend post-transfusion follow up visits at 5-7 and 28 days after the last study transfusion for routine safety labs, immune reactivity test to IBS RBC and to obtain samples for CHIKV, DENV and ZIKV viremia (blood and urine by RT-PCR), DENV/ZIKV/CHIKV serology (IgM/IgG and confirmation with the plaque reduction neutralization test [PRNT] or Reporter Virus Particles [RVP] when antibodies are detected/increasing) and antibody assessment. A final blood sample for immune reactivity test to IBS RBC will be collected 75 days after the last study transfusion. Study procedures are summarized as follows: Screening/Recruitment All potentially eligible patients at participating institutions will be approached for study consent prior to RBC transfusion. Patients who consent to the study will be assigned a study ID number and undergo screening. Screening data collection and procedures will include: Demographics (age, sex), vital signs, height, weight, indication for anticipated transfusion, type of scheduled surgery (if applicable), medical and surgical history, transfusion history, physical examination, comorbid conditions, concomitant medications, hematology panel (including complete blood count, blood type, blood chemistry, coagulation panel, DAT test, immune reactivity to IBS RBCs, pregnancy test [when applicable]), Blood and urine samples will also be taken and archived for future testing for viral RNA and/or antibodies for ZIKV, CHIKV and DENV. Positive ZIKV/CHIKV/DENV serology will be further investigated for IgG and IgM, as well as confirmation with PRNT or RVP when antibodies are detected). Randomization and Blinding Eligible patients will be enrolled in the study and will be considered for randomization. If a patient is enrolled and receives a RBC transfusion prior to randomization, that patient will no longer be considered for randomization, and their participation in the study will end. An Interactive Web Response System (IWRS) will be used for electronic randomization of eligible patients. Randomization will be at a 1:1 ratio of Test: Control and stratified by site and baseline bleeding status [indication for RBC transfusion due to active bleeding (WHO grade 3 or 4, Appendix 5) or for anemia without active bleeding]. Randomized patients who do not receive any study RBC transfusions through 28 days after randomization will be discontinued/withdrawn from the study and replaced. Additional data will not be collected for these patients. At enrollment, the patient's eligibility status will be entered into the electronic data capture system (EDC). If eligible, the patient will be randomized. Only appropriate blood bank staff will be able to access the treatment arm assignment. Study RBC unit labels will be indistinguishable for Test and Control products. Medical staff, and others caring for participating patients, as well as the sponsor (and delegates) will be blinded to treatment assignment. Unblinded delegates will monitor the production of the RBC components. Treatment Patients will be transfused with Test or Control RBC components for up to 28 days. An RBC transfusion episode will be defined as all RBC units transfused within 4 hours. A confirmed negative immune reaction to IBS RBC is required prior to the first study transfusion. Compatibility for RBC antigens will be confirmed using site's SOPs prior to transfusion of IBS RBCs. In case of confirmed physiologically active antibodies to IBS RBC or any presumed or documented antibodies to IBS RBC that preclude further transfusion with IBS RBCs, patients will be discontinued/withdrawn from the study and supported with locally sourced and ZIKV-screened RBC components; if not available locally, components may be imported from ZIKV non-epidemic regions. Study Assessments: Monitoring and Follow-up Acute Transfusion Support Period (First study transfusion through Day 28 or death) The acute transfusion support period will comprise 28 days from the day of the first study transfusion through Day 28, or death of a patient. During this period, patients will receive as many study RBCs as deemed appropriate by the treating physician. All AEs, SAEs, TRs and unanticipated adverse device effects will be collected starting from the initiation of the first study transfusion through the entire transfusion support period (and through 28 days after the last study transfusion). The Investigators will assess each AE/SAE/TR and unanticipated adverse device effects for relation to the transfusion study RBCs. Transfusion reactions will be classified by the definitions in the CDC NHSN Hemovigilance Module Surveillance Protocol (Appendix 1) and will be captured in the eCRF and in the CDC NHSN Biovigilance Component/Hemovigilance Module (www.cdc.gov/nhsn). Most proximate vital signs in the medical record will be collected prior to and following each study transfusion. All concomitant medications taken during the study and blood products transfused will be recorded on the EDC system with indication, total daily dose, and dates of drug administration. During the acute transfusion support period, patients will undergo the following assessments prior to transfusion, at any time that 5 days have elapsed since the last study transfusion or at death: vital signs, AEs, TRs, SAEs and unanticipated adverse device effects, comorbid conditions, blood samples for safety labs (complete blood count, blood chemistry panel, coagulation panel), DAT test, ZIKV/DENV/CHIKV viremia (blood and urine by RT-PCR) and DENV/ZIKV/CHIKV serology (IgM/IgG and confirmation with PRNT/RVP when antibodies are detected/increasing), and immune reactivity to IBS RBCs.. Samples may be used for additional in vitro research tests as required to confirm suspected ZIKV, CHIKV and DENV or other transfusion-transmitted pathogen mediated infections. Follow-Up Period (5, 28 and 75 days after last study transfusion) For the purposes of the Day 5-7, Day 28 (± 7 days) and Day 75 (± 15 days) follow-up visits, Day 1 of the follow-up period is the first day after the last study transfusion Day 5-7 and Day 28 After the Last Study Transfusion (± 7 days) Five to seven (5-7) and 28 (± 7) days after the last study transfusion, blood samples will be collected for routine safety labs, for assessment of ZIKV/DENV/CHIKV viremia and ZIKV/DENV/CHIKV serology and for immune reactivity test for IBS RBC; a blood and urine sample will also be collected for ZIKV/DENV/CHIKV viremia assessment. All AEs, SAEs, TRs and unanticipated adverse device effects will be reviewed and recorded for the period from the first study transfusion through Day 28 after the last study transfusion. End of Study Visit (Day 75 ±15 days) At Day 75 (± 15 days) after the last study transfusion, a blood sample will be collected for immune reactivity test for IBS RBC. Stage B Upon review and approval by FDA, all eligible patients who provide consent at participating sites will be transfused with IBS RBCs according to local practices for as long as needed during the duration of the study. A confirmed negative crossmatch with IBS RBC is required prior to every study transfusion. Compatibility for RBC antigens will be confirmed according to site's SOPs prior to transfusion of IBS RBCs. In case of confirmed physiologically active antibodies to IBS RBC, patients will be discontinued from the study and supported with conventional RBCs, locally sourced and ZIKV-screened. Transfusion reactions and SAEs occurring through 28 days post transfusion will be documented. A serum sample for antibodies specific for IBS RBC associated antigens and a blood sample for archival testing for viral RNA and/or antibodies for CHIKV, DENV and ZIKV will be taken before and 28 days after the first study transfusion (±7 days) until data are available for at least 1000 participants.

Clinical Study Identifier: NCT03037164

.

Contact Investigators or Research Sites near you

Start Over

Please choose location

View all locations

Lumen Vera, Dr.

Menonita General Hospital
Aibonito, Puerto Rico
  Connect »

Jose R Ramirez-Vazquez, Dr.

HIMA San Pablo Hospital
Caguas, Puerto Rico
  Connect »

Edgardo Cartagena, Dr.

San Juan Bautista School of Medicine Clinical Research Unit
Caguas, Puerto Rico
  Connect »