Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT03459287 |
| Other study ID # |
CLI 00125 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
December 5, 2018 |
| Est. completion date |
September 30, 2024 |
Study information
| Verified date |
February 2024 |
| Source |
Cerus Corporation |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The objective of this study is to evaluate the efficacy and safety of RBC transfusion for
support of acute anemia in cardiovascular surgery patients based on the clinical outcome of
renal impairment following transfusion of red blood cells (RBCs) treated with the INTERCEPT
Blood System (IBS) for Red Blood Cells compared to patients transfused with conventional
RBCs.
Description:
This is a prospective, multicenter, randomized, double-blinded, active controlled,
parallel-design, non-inferiority study.
Screening/Recruitment
In order to minimize the number of patients who enroll in the study but do not require RBC
transfusion, only patients with a relatively high likelihood to receive a RBC transfusion as
determined by the Investigator (e.g., patients receiving aspirin, clopidogrel (or analogs)
and/or GPIIb/IIIa inhibitors), or patients with a TRUST Score of ≥3 will be eligible for
enrollment. Patients ≥11 years of age undergoing complex cardiac surgery may be identified
through pre-operative scheduling procedures in advance of their surgery.
Patients undergoing urgent or emergent cardiac surgery are eligible for the study, subject to
institutional review board (IRB) approval of an appropriate informed consent process.
All potentially eligible patients will be approached for study consent/assent within 30 days
prior to their surgical procedure. Subjects who consent/assent to the study will be assigned
a subject ID number and undergo screening.
Screening will include documentation of the patient's pre-surgical exposure to radiographic
contrast media and number of prior pregnancies (females). Screening data may be derived from
the medical record when performed within 30 days prior to their surgical procedure.
Eligibility status and other study data including all TRUST components will be entered into
the clinical database via an electronic data capture (EDC) system using electronic case
report forms (eCRFs). Patients who fail eligibility for any or multiple inclusion/exclusion
criteria may be rescreened for eligibility closer to the time of surgery.
Randomization and Blinding
Eligible subjects will be randomized up to 7 days before or on the day of scheduled surgery
(Day 0). An Interactive Web Response System (IWRS) will be used for electronic randomization
of eligible patients. Randomization (in 1:1 ratio for Test:Control) stratified by site,
pre-existing renal impairment (baseline sCr ≥1.2 mg/dL vs. < 1.2 mg/dL), and cardiac surgery
group (more at risk for renal complications vs. less at risk) will be employed. Screened
subjects who receive a red cell transfusion prior to randomization will no longer be
considered for randomization, and their participation in the study will end. Patients may be
rescreened for eligibility closer to the time of surgery.
Treatment
Once a subject is randomized, only study RBCs (Test or Control, per the subject's
randomization) should be dispensed and transfused during the acute transfusion support period
(Day 0 to Day 7 post surgery, hospital discharge, or death, whichever is first), as
clinically indicated and determined by the treating physician.
In rare exceptions where study RBCs are unavailable or patient's need for RBC transfusions
exceeds the quantity of study RBCs in inventory at the hospital blood bank (e.g., during a
Massive Transfusion Protocol), a transfusion using non-study RBC (conventional) may be given
to provide the patient with an appropriate and necessary treatment. In this case, a protocol
deviation should be documented. If a study RBC transfusion is given after randomization
before surgery commences, a protocol deviation should also be documented.
Treatment assessments will be divided into an acute transfusion support period starting the
day of surgery (Day 0 up to Day 7) during which study RBC (Test or Control) are administered,
a post-surgical follow-up period of a minimum of 28 days after the last study transfusion to
collect additional safety data, a clinical assessment at day 30 after surgery specifically
for mortality and RRT status, and a visit at day 75 (±15) after the last study transfusion to
assess mortality and RRT status, and collect samples for serological screening for antibodies
specific to INTERCEPT RBCs.
In all patients, anesthesia and surgical procedures will be performed according to the local
standards of care. Following the acute transfusion support period, subjects may receive
conventional RBC components if additional transfusions are needed, as indicated by their
treating physician.
Study Assessments: Monitoring and Follow-up
Baseline through Acute Transfusion Support Period (Pre-Op Day -1 up to Post-Op Day 7):
A screen for antibodies specific for INTERCEPT RBCs should be performed every time that a
routine IAT is performed during the acute 7-day study transfusion period.
A blood sample for sCr will be taken at 48 ±4 hours after completion of surgery for both
transfused and non-transfused subjects., A sCr will be determined on a daily basis during the
acute transfusion support period up to 7 days post-surgery. Other parameters including
additional sCr will be collected on eCRFs only when available in the medical record.
Randomized subjects who do not receive an RBC transfusion following randomization within the
first 48 hours after surgery will be discontinued from the study and replaced.
Daily sCr assessments will be recorded up to and including 48 ±4 hours for transfused and
non-transfused subjects. Other post baseline laboratory parameters and adverse events (AEs)
will not be collected for non-transfused subjects. Vital status will be reported for
randomized and non-transfused subjects at the time of discontinuation.
Hemodynamic and laboratory measures will be assessed pre-operatively (Day -1, Baseline) and
daily as available in the medical record from post operative Day 1 through Day 7, hospital
discharge or death, whichever occurs first. If a subject is discharged prior to Day 7 but
returns to the study site for a standard of care visit on Day 7, blood samples should be
obtained on that day for a complete blood count and sCr determination.
Hemodynamic parameters that will be collected if available, include heart rate, blood
pressure, mean arterial pressure, central venous pressure (CVP), and peripheral oxygen
saturation via pulse oximetry probe.
Laboratory parameters that will be captured on eCRFs include BUN, creatinine (sCr), AST, ALT,
fibrinogen, bilirubin, troponin, hemoglobin, and platelet counts.
Transfusion reactions (TRs), adverse events (AEs) and serious adverse events (SAEs) will be
assessed on a daily basis and documented in the eCRF from the start of surgery or the start
of the first study transfusion (whichever is first) through post-operative Day 7 and as
available through day 28 after the last study transfusion. Vital status will be reported for
randomized and non-transfused subjects at the time of discontinuation.
NOTE: The following applies to randomized transfused subjects only.
Post-operative Day 8 (or Post-discharge, if earlier) through 28 Days After Last Study
Transfusion:
Subjects will be monitored for TRs, AEs and SAEs following the 7-day acute transfusion
support period, through 28 days after the last study transfusion or death, whichever occurs
first, according to the local standard of care. In an outpatient setting, weekly telephone
surveillance calls to the subject will be performed in order to collect safety events until
the next follow-up visit.
28 (±3) Days After Last Study Transfusion or Premature Discontinuation from study:
Subjects who have been discharged should be scheduled for the follow up visit 28 (±3) days
after the last study transfusion to obtain additional safety information, including
patient-reported AEs/ SAEs; laboratory results including sCr, DAT/ IAT; a sample for HLA
antibodies and antibodies specific to INTERCEPT RBCs will be obtained. All randomized
subjects who receive any study RBC transfusion must have their vital status documented at
this visit, or earlier, if the subject dies prior to the visit. If a subject has been
discharged, other safety information (e.g., AEs and SAEs) may be obtained through medical
records, the subject's physician, or a telephone interview with either the subject or a
family member.
30 Days After Surgery:
All randomized subjects who receive a study RBC transfusion must have their vital status and
need for RRT (defined as hemodialysis or peritoneal dialysis) documented at Day 30 after
surgery. RRT that is provided prophylactically during surgery while patient is on a bypass
machine (the pump), does not meet this endpoint. The vital status and RRT assessment on Day
30 can be performed either from the medical records, from a phone call to the subject or
family, or during the visit 28±3 days after the last study transfusion (only if the last
study transfusion was given at day 2 or later in the acute transfusion support period).
End of Study: 75 (±15 Days) After last Study Transfusion:
75 (±15) days after the last study transfusion (End of Study), serum samples for antibodies
specific for INTERCEPT RBCs will be obtained, either in hospital, at a clinic visitor or
offsite. Mortality and the need for RRT will be assessed
Data and Safety Monitoring Board (DSMB)
The study data and safety will be monitored by an independent Data and Safety Monitoring
Board (DSMB). The primary mission of the DSMB is to ensure patient safety and protocol
compliance for data collection. The DSMB will be assembled by the Sponsor and composed of
transfusion medicine and other experts as per the DSMB charter. DSMB members will be
independent of the Sponsor.
Interim Analysis and Early Stopping Rule
Aside from the blinded interim analysis for sample size re-estimation performed in October
2021, no other interim analysis is planned for this study to compare treatment differences
with respect to efficacy or safety at any time prior to the completion of the study. Specific
stopping rules, defined for safety considerations, are defined in Section 4.6 of the
protocol.
