Acute anemia secondary to cardiovascular surgery. MedDRA version: 14.1 Level: LLT Classification code 10054312 Term: Anemia postoperative System Organ Class: 10022117 - Injury, poisoning and procedural complications
Conditions
Interventions
Product Name: S-303 Treated Red Blood Cells in SAG-M
Product Code: Not applicable
Pharmaceutical Form: Infusion
INN or Proposed INN: Amustaline dihydrochloride
CAS Number: 210584-54-6
Current Sponsor
Sponsors
Cerus Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The study will enroll sufficient patients to obtain at least 50 patients with acute anemia who receive at least one RBC component of the assigned treatment type by transfusion during or following an elective cardiac surgery procedure. In order to minimize the number of patients who enter the study but are not evaluable because they do not receive an RBC transfusion, only patients with a relatively high probability for RBC transfusion will be enrolled. The Transfusion Risk Understanding Screening Tool (TRUST) Score has been validated to predict the likelihood of RBC transfusion in this population. For this study, only patients with a high probability to receive a transfusion as determined by the Investigator OR patients with a TRUST Score of 3 or greater will be eligible for enrollment. The TRUST Score (Alghamdi 2006) is an integer from zero to eight (inclusive); one point is assigned for each of the following elements: • Hb 65 years • Non-elective surgery • Serum Cr > 1.36 mg/dL • Previous cardiac surgery • Non-isolated surgical procedure INCLUSION CRITERIA: 1. Must be age 18 years or older 2. Must be willing to use an acceptable form (as approved by the Investigator or designee) of contraception while on study 3. Must be readily available by telephone 4. Must be willing to participate in the second 6MWT at 7 to 10 days after discharge 5. Must provide an informed consent for study participation and have signed an EC-approved informed consent 6. Must have a negative crossmatch to S-303 treated RBCs at study entry 7. Must have a blood type of either A+ or O+ 8. Patients must have a likelihood of receiving a transfusion as determined by the Investigator OR a TRUST Score of =3 at study entry 9. Must be scheduled to receive one of the following operative procedures: •Coronary artery bypass graft only, first procedure. •Valve repair or replacement only, first procedure. •A combination of first time CABG and valve repair or replacement. After consultation with the Medical Monitor, provision can be made to enroll patients who may meet these general criteria but whose surgical procedure is not precisely described in the above categories. Such patients will be classified as “other” with their explicit condition reported with other study data. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 50 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: Any of the following criteria will exclude a potential patient from participation in the study: 1. A positive pregnancy test result 2. Inability of patient to comply with the protocol in the opinion of the Investigator or attending physician 3. Breast-feeding of an infant or child 4. Active autoimmune hemolytic anemia, or a positive Direct Antiglobulin Test (DAT) result 5. Treatment with any medication that is known to adversely affect red blood cell viability 6. Emergent or salvage surgical status at the time of surgery defined as follows: •Presence of ongoing ischemia including angina at rest despite maximal medical therapy. •Acute evolving myocardial infarction within 24 hours before surgery. •Pulmonary edema requiring intubation. •Presence of shock or hemodynamic instability with or without circulatory support. •Systolic blood pressure < 80 mm Hg and/or Cardiac Index < 1.8 despite medical intervention (intravenous inotropes or similar pharmacologic agents). •Cardiopulmonary resuscitation in the 24 hours prior to surgery or anesthesia induction. •Requiring an intra-aortic balloon pump or ventricular assist device. 7. Participation in any one of the following types of clinical studies either concurrently or within the previous 28 days: investigational blood products, pharmacologic agents or imaging materials, including dyes, investigational surgical techniques, or devices. Studies of nutrition, psychology, or socioeconomic issues are not grounds for exclusion 8. Current diagnosis of either chronic or acute renal failure (requiring dialysis) OR a serum creatinine greater than or equal to 1.8 mg/dL within 30 days prior to the start of surgery 9. Current diagnosis of either chronic or acute hepatic insufficiency OR a total serum bilirubin greater than or equal to 2.0 mg/dL within 30 days prior to the start of surgery 10. Pre-existing RBC antibody that may make the provision of compatible study RBC components difficult 11. A positive cross match to S-303 treated RBC
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The study is designed to support CE Mark registration for the S-303 Treatment System for Red Blood Cells. The two major objectives are: (1) In vitro analysis of RBCs: the primary outcome measure is the mean hemoglobin (Hb) content per manufactured RBC unit in each treatment group assessed by a statistical hypothesis of equivalence. The Hb mass available for transfusion in each RBC unit is correlated with the magnitude of the potential post transfusion Hb increment and therefore represents one measure of efficacy. (2) A clinical transfusion study in at least 50 cardiovascular surgery patients to obtain an initial assessment of the therapeutic efficacy of Test RBC units in comparison to Control RBC units. Three exploratory clinical outcome measures will be compared between the Test and Control treatment groups: a) Incidence of renal insufficiency b) Incidence of hepatic insufficiency c) Overall cardiopulmonary function ;Secondary Objective: This clinical transfusion study also includes a full safety assessment. The results of this study will facilitate the design of a future more substantial clinical trial in the same patient population to support specific blood product registrations using the device. ;Primary end point(s): The primary endpoint of the study, consistent with the device-classification for the CE Mark registration, is the comparison of mean hemoglobin content per RBC component between the Test and Control groups. The hypothesis of interest is that the mean hemoglobin content is essentially equivalent, that any difference is of no clinical consequence, between the treatment groups.;Timepoint(s) of evaluation of this end point: Hemoglobin measurement will occur at production of each RBC unit. However, the comparison evaluation of mean hemoglobin content per RBC unit between the Test and Control groups will be performed at end of study, after a sufficient quantity of analyzable RBC units (at least 200 per treatment group) have been prod | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints include assessments of relevant in vitro characteristics of RBC components that correlate with therapeutic efficacy: •Proportion of RBC components that meet the EU guideline for hemoglobin content, hematocrit, and hemolysis at the end of storage •Proportion of RBC components that have ATP levels of >2 micromol/L at 35 days of storage •Proportion of RBC components that have plasma-free hemoglobin levels corresponding to < 0.8% hemolysis after 35 days of storage ;Timepoint(s) of evaluation of this end point: In vitro measurements for characterization of RBC components will occur at the end of RBC storage (Day 35). However, evaluation of the proportion of RBC components that meet the EU Guidlines or pre-specified criteria will be performed at end of study. | — |
Countries
Germany
Contacts
Public ContactMegan Le Ward, Regulatory Affairs
Cerus Corporation
Outcome results
None listed