A Randomized, Controlled, Phase I Clinical Trial to Assess the Safety of Whole Blood Treated With Amustaline (S-303) and Glutathione (GSH), a Pathogen Reduction System, in Anemic Patients
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 发起方
- 主要终点
- Severe Transfusion Reactions
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must be18 years of age or older;
- •Patients should have poorly tolerated anemia with a hemoglobin level greater than or equal to 5.0 g/dl and less than or equal to 7.0 g/dl. At the discretion of the investigator, inclusion is possible at a hemoglobin level greater than 7.0 g/dl if the criteria in the current local guidelines are met.
- •Patients must sign the study's informed consent form prior to initiation of any study-specific procedure / treatment. Enrolled patients may give additional consent for specimens collected during this study to be used for future research on TTIs. Patients may participate in the main trial and decline collection of specimens for future research.
- •Patients must agree to be hospitalized for a maximum of 72 hours after initiation of a study transfusion;
- •Female patients of childbearing potential must:
- •have a negative serum pregnancy test within 72 hours prior to receiving the first study blood to rule out pregnancy, and;
- •use at least one method of birth control that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly. These include combined oral contraceptives, implants, injectable, some intrauterine devices, sexual abstinence or vasectomized partner. The selected method must be used for the duration of study participation that means from day 1 (day of initiation of study transfusion) until day 58 (Final Study Visit).
排除标准
- •The presence of any one of the following exclusion criteria will lead to exclusion:
- •Patients with blood group AB and blood group O Rhesus negative (due to concern of limited supply).
- •Positive antibody screening reaction specific to red blood cells treated with amustaline and glutathione (GSH).
- •Positive red cell alloantibody screening (IAT) / presence of red cell antibodies;
- •Patient has ongoing clinical-significant bleeding described as grade 2 or more according to the U.S. National Cancer Institute's CTCAE v5.0 severity grading scale.
- •Lifelong history of major bleeding due to congenital or acquired coagulopathy.
- •History of thrombosis or thromboembolic events.
- •Blood in feces or hemoglobinuria in the last 30 days.
- •Pre-transfusion thrombocyte counts of < than 50 Giga/l (x109).
- •Oral, intravenous or sub-cutaneous prophylactic or therapeutic anticoagulants.
- •Central body temperature increase of ≥2°C within 24 hours before transfusion.
- •Clinical signs of ongoing sepsis including fever >39°C with signs of a systemic, inflammatory response.
- •Abnormal activated partial thromboplastin time (aPTT) and/or abnormal prothrombin time (PT) or INR laboratory results
- •Transfusion of a blood product within 2 weeks prior to enrollment.
- •Abnormal total bilirubin (≤ 2 x upper limit of normal) levels and/or clinical signs of jaundice.
- •Sickle cell anemia.
- •Malignant cancer patients having received chemotherapy within 12 months.
- •Patients in need of multiple RBC or WB transfusions in the first 24 hours according to the investigator's judgment (i.e., more than one product).
- •Pregnant or breast-feeding.
- •Inability to comply with the protocol in the opinion of the investigator.
- •Participation in any other type of clinical study, either concurrently or within the previous 30 days, including: investigational blood products, nutrition, pharmacologic agents or imaging materials, including dyes, investigational surgical techniques, or devices. Studies of psychology or socioeconomic issues are not grounds for exclusion.
- •Participation on not more than two research studies per year.
结局指标
主要结局
Severe Transfusion Reactions
时间窗: 24 hours
The primary safety outcome will be assessed by the occurrence of transfusion reactions \>= grade 2 according to the Swissmedic transfusion reaction grading and causality criteria (Appendix 1: Swissmedic Classification and Analysis of Transfusion related reactions ), during the first 24 hours following administration of each study transfusion, with probable, possible or certain causality to the transfused product.
次要结局
- Adverse Events(28 days (+/-3 days))
- Treatment-induced antibodies(58 days (+/-7 days))
- Treatment-induced auto-antibodies(58 days (+/-7 days))
- 24 h post-transfusion hemoglobin(24 hours)