Clinical Trial Details
— Status: Withdrawn
Administrative data
| NCT number |
NCT04020224 |
| Other study ID # |
1702005 |
| Secondary ID |
|
| Status |
Withdrawn |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
January 2024 |
| Est. completion date |
March 2025 |
Study information
| Verified date |
March 2024 |
| Source |
Swiss Transfusion SRC |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The pathogen reduction system for whole blood using amustaline (S-303) and glutathione (GSH)
hast a potential to decrease transfusion-transmitted infection. There is a scientific basis
to hypothesize, that cells containing DNA and RNA such as bacteria, viruses and parasites
that could be present in blood collected from asymptomatic infected donors are inactivated in
the treated whole blood and therefore reduce the risk of transfusion-transmitted infections.
The aim of the study is to assess the safety of whole blood treated with amustaline and
glutathione and transfused in patients with anemia.
This is a first-in-human-subjects study. Whole blood (WB) products treated with the
amustaline (S-303) and glutathione (GSH) pathogen reduction technology have not been
evaluated in human beings. However, red blood cells concentrates treated with amustaline and
GSH have been evaluated in multiple clinical studies.
The study described in this protocol is a randomized, controlled, open-label Phase I clinical
trial.
20 patients will be randomized into either the Test or Control arm in a ratio of 1:1.
10 patients assigned to the Test arm will receive one amustaline/GSH treated whole blood
product.
10 patients assigned to the Control arm will receive the Standard of Care (SOC), either one
red blood cell (RBC) component or one whole blood product.
Description:
Screening:
All potentially eligible patients at the participating institution will be approached for
study consent prior to study transfusion. Enrolled patients will also be asked for consent to
the storage of their samples for future research on Transfusion Transmitted Infections (TTI).
Illiterate patients can be consented by an impartial witness (see section 2.7).
Patients who consent to the study will be assigned a study identification (ID) number and
undergo screening.
Screening data collection and procedures will include: Demographics (age, sex), vital signs,
height, weight, indication for anticipated transfusion, medical history including history of
bleeding and transfusion and concomitant medications. A physical examination, including skin
inspection, will be performed. Blood samples will be drawn for a hematological panel
(including complete blood count, blood chemistry, blood type, coagulation (aPTT, PT and/or
INR) and pregnancy test (if applicable). Immunohematology tests will be performed on a
patient's sample at the blood center. This includes a Direct Antibody Test (DAT), immune
reactivity to RBCs that have been processed with amustaline and glutathione, red cell
alloantibody screen (Indirect Antibody Test (IAT) / Indirect Coombs).
Blood samples (pre/post-treatment) for future research on TTIs will be archived in a biobank
of the Institut Pasteur de Côte d'Ivoire (IPCI) (see section 9.3.3.11).
Randomization:
After successful screening, eligible patients will be assigned to a treatment arm by
randomization. Randomization will be performed in the blood center by sequentially selecting
a randomization envelope starting with the lowest number (e.g., 1 for the first eligible
subject in ascending order up to envelope number 20 for the 20th subject).
The ratio of patients assigned to the Test and Control group will be 1:1. Each subject will
receive a Test product or an untreated product based on existing SOC. The assigned blood
product number must be noted on the randomization assignment envelope and on the release
form. The product number will also be entered into the case report form (CRF).
The replacement strategy in this Phase I clinical trial is based on the aim to reach twenty
evaluable patients. "Evaluable patients" is defined as those patients who are randomized and
receive any study transfusion.
If a randomized subject withdraws or is withdrawn from the study prior to the administration
of any study transfusion, or does not receive any study transfusion through 7-days
post-randomization, this subject will be replaced by the next eligible subject using the same
randomization envelope. If a randomized subject receives a conventional (untreated) blood
transfusion prior to study transfusion, the patient will be replaced as described above.
All patients who received at least one investigational product will be included in the
analysis (i.e., group of 20 evaluable patients) and followed through the final Day 58 study
visit).
All used and unused randomization envelopes will be kept in the Site File for reconciliation.
Pre-transfusion visit:
Vital signs, weight, skin inspection will be performed, hemoglobin will be assessed, and
urine samples will be taken for detection of blood in urine. If the patient consents to
future research on TTI, a sample will be drawn and sent to the archival biobank.
Treatment:
Patients will be transfused with one investigational product or SOC on Day 1. In case he or
she requires further transfusion support to treat anemia, enrolled patients may be treated
with a second study transfusion. A patient who requires a second blood component within the
first 24 hours will receive a second treatment, if available, with an investigational product
from the assigned treatment arm. This patient will be included into the analysis of evaluable
patients and followed up to Day 58, the final study visit. If the patient requires further
transfusions (third transfusion etc.) it will be SOC.
Post-transfusion visit(s):
Patients will be hospitalized for 24 hours after each study transfusion to allow close
monitoring and data collection uniquely for the study purpose since their condition would
allow an outpatient treatment. 3 hours and 6 hours after initiating each study transfusion
vital signs and skin inspection will be performed.
24-hours post-transfusion vital signs, urine dipstick, concomitant medication/intervention
will be assessed, laboratory blood samples for hemoglobin, coagulation assays (aPTT, PT
and/or INR) and potassium and a sample for determination of residual S-300 will be taken.
If a subject consented to future research on TTI, a second blood sample (post-transfusion)
will be collected and archived in the biobank.
In case clinical symptoms of transfusion-related bacterial contamination occur, a blood
sample will be collected during the post-transfusion period and microbiological analysis will
be performed according to standard procedures in the IPCI. Those patients will be treated
according to SOC.
Interim Safety Follow-up visit Day 14 days (+/-3 days) after last study transfusion: adverse
event and and concomitant medication.
Final Safety Follow-up visit Day 28 days (+/-3 days) after last study transfusion:
At day 28 (+/-3 days) a physical examination, vitals, urine dipstick and blood samples will
be collected for laboratory analysis of safety variables (e.g., complete blood count,
coagulation) and urine dipstick.
All Adverse Events (AE), Transfusion Reactions (TR) 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.
The Investigators will assess each AE for relation to the study transfusion. Available
clinical diagnostic tools will be used to rule out unrelated AEs and to classify possible,
probable and certain TRs using Swissmedic causality definitions.
Final study visit on Day 58 (+/-7 days) after last study transfusion) At the final study
visit, the immune reactivity of patient serum to RBCs treated with amustaline/GSH for
patients in the test arm and a DAT test for all patients will be performed.
Serious Adverse Events (SAEs) will be reviewed and recorded for the full study period from
transfusion through to Day 28, which is the day of the final safety follow-up study visit.
The Investigators will assess each SAE for relation to the study transfusion. As SAEs will be
further evaluated as possible transfusion reactions. SAEs that are determined to be possibly,
probably or certainly related to the transfusion will be classified as TRs.
