A Phase 3 interventional study of Liberal Red blood cell transfusion and Restrictive Red blood cell transfusion in Septic Shock, Anemia and Cancer, sponsored by Assistance Publique - Hôpitaux de Paris. Completed at 20 sites in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-06-25.
Sponsored by Assistance Publique - Hôpitaux de Paris · Phase 3, Interventional, and Treatment
Septic shock is a frequent complication associated with high mortality in patients with malignancies. The best transfusion strategy (restrictive or liberal) for the resuscitation of septic shock remains a controversial issue, in relation with potentially discrepant goals of tissue oxygenation and transfusion sparing.
In this study, the investigators propose to address the efficacy of two RBC transfusion strategies (liberal or restrictive) in restoring appropriate tissue oxygenation as well as their tolerance.
The investigators designed a prospective randomized multicenter trial aimed at comparing liberal and restrictive RBC transfusion strategies applied during the first 48 hours of resuscitation in cancer patients with septic shock and anemia.
Septic shock is a frequent complication in patients with malignancies and remains affected with a mortality rate higher than 50%.
Red blood cell (RBC) transfusion remains a major issue for critically ill cancer patients who frequently display anemia as a result of malignant bone marrow involvement or imposed by cytotoxic treatments. However, our current practice of RBC transfusion in the intensive care unit (ICU) is drawn from general populations. Several case-control studies suggested that RBC transfusion was associated with higher mortality and increased incidence of ICU-acquired complications in critically ill patients. In 1999, a restrictive strategy of non-leucodepleted RBC transfusion to maintain hemoglobin above 7 g/dL was shown to be as effective as a liberal transfusion strategy aimed to maintain haemoglobin > 10 g/dL in critically ill patients. As of today, the current recommendations for RBC transfusion remain largely based on this study which excluded patients with a history of anemia. Leucodepletion that is now routinely implemented in France might be associated with fewer transfusion-related events. Indeed, some recent studies challenged the restrictive strategy and suggested that a higher transfusion threshold might be beneficial in septic patients for whom oxygen delivery is of paramount importance. Most importantly, a hemodynamic support algorithm for severe sepsis also known as early goal-directed therapy (EGDT) included a hematocrit target of 30%. The majority of EGDT-treated patients received RBC transfusion within the early 72 hours of resuscitation, thereby representing a major difference compared to standard treatment, but the prognostic value of RBC transfusion was not specifically assessed. A recent case-control study also suggested that RBC transfusion was an independent predictor of survival in patients with septic shock.
Cancer patients with septic shock and hemoglobin level \< 9 g/dL initiation will be randomized to the interventional arm (liberal transfusion strategy to maintain hemoglobin > 9 g/dL) or to the control arm (restrictive transfusion strategy to maintain hemoglobin > 7 g/dL) in a 1:1 ratio.
Patients from the intervention arm will have their hemoglobin level maintained above 9 g/dL for the whole time under vasopressors, for a maximum of 28 days. After weaning from vasopressor, the transfusion threshold will be lowered to 7 g/dL as recommended by the SSC guidelines. In case of shock relapse requiring reintroduction of vasopressors, the transfusion threshold will be upgraded back to 9 g/dL until next catecholamine weaning.
In the control arm, the transfusion threshold will be 7 g/dL until ICU discharge regardless of catecholamine administration.
The primary objective of the study will be the restoration of tissue oxygenation as assessed by lactate clearance at 12 hours following randomization. The secondary endpoints will be related to restoration of tissue oxygenation at alternative time points (6h, 24h, 36h, 48h) as assessed as above, the 7-day, 28-day, in-ICU and in-hospital mortality rate, changes in organ failures over the first 48 hours and 7 days, duration for organ failure supports, the development of acute ischemic and thrombotic events (myocardial infarction, mesenteric ischemia, ischemic stroke, limb ischemia, deep venous thrombosis) over the first 7 days.
An interim analysis on the primary endpoint has been pre-planned at the end of the follow up of half of patients included.
890 studies on the registry are indexed under Shock, Septic; 210 are open to participants now.
This study's enrollment of 192 is above the median of 78 across 547 interventional studies indexed under Shock, Septic.
Browse Shock, Septic studies →Assistance Publique - Hôpitaux de Paris is the lead sponsor of 3,576 studies on the registry; 1,028 are open to participants now.
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Exclusion Criteria:
Maintain a hemoglobin level \> 9 g/dL during the first 48 hours of resuscitation of septic shock
Biological: Liberal Red blood cell transfusion
Maintain a hemoglobin level \> 7 g/dL during the resuscitation of septic shock
Biological: Restrictive Red blood cell transfusion
Hemoglobin level will be maintained above 9 g/dL (liberal strategy) for the first 48 hours following randomization. After 48 hours, indications of RBC transfusions will be at the discretion of attending physicians in patients with persistent circulatory failure. After resolution of acute circulatory failure, a 7 g/dL transfusion threshold will be recommended regardless of the allocation arm. In case of subsequent episodes of septic shock, the transfusion strategy will be at the discretion of attending physicians
Hemoglobin level will be maintained above 7 g/dL (restrictive strategy) during all the stay in ICU
Tissue oxygenation
Percentage of patients with normal arterial lactate level at 12 hours (\<=2 mmol/L) or a relative decrease (or clearance) of arterial lactate level above 30% according to the formula (lactateH0 - lactateH12)/lactate H0\*100. lactateH0 : arterial lactate level at inclusion lactateH12 : arterial lactate level at 12h
Time frame: 12 hours
Tissue oxygenation 6
Percentage of patients with normal arterial lactate level at 6 hours (\<=2 mmol/L) or a relative decrease (or clearance) of arterial lactate level above 30% according to the formula (lactateH0 - lactateH6)/lactate H0\*100. lactateH0 : arterial lactate level at inclusion lactateH6 : arterial lactate level at 6h
Time frame: 6 hours
Tissue oxygenation 24
Percentage of patients with normal arterial lactate level at 24 hours (\<=2 mmol/L) or a relative decrease (or clearance) of arterial lactate level above 30% according to the formula (lactateH0 - lactateH24)/lactate H0\*100. lactateH0 : arterial lactate level at inclusion lactateH24 : arterial lactate level at 24h
Time frame: 24 hours
Tissue oxygenation 48
Percentage of patients with normal arterial lactate level at 48 hours (\<=2 mmol/L) or a relative decrease (or clearance) of arterial lactate level above 30% according to the formula (lactateH0 - lactateH48)/lactate H0\*100. lactateH0 : arterial lactate level at inclusion lactateH48 : arterial lactate level at 48h
Time frame: 48 hours
Mortality 7
Percentage of Death at 7 days
Time frame: 7 days
Mortality 28
Percentage of Death at 28 days
Time frame: 28 days
ICU mortality
Percentage of Death in ICU at 28 days
Time frame: 28 days
Hospital mortality
Percentage of Death in Hospital at 28 days
Time frame: 28 days
Change in SOFA 24
Differences between SOFA score at inclusion (SOFA0) and SOFA score at 24 hours. The sequential organ failure assessment score (SOFA score) ranges from 0 (normal patient) to 24 (most severe patient). Vincent JL, de Mendonça A, Cantraine F, et al. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on "sepsis-related problems" of the European Society of Intensive Care Medicine. Crit Care Med. 1998;26(11):1793-800.
Time frame: 24 hours
Change in SOFA 48
Differences between SOFA score at inclusion (SOFA0) and SOFA score at 48 hours. The sequential organ failure assessment score (SOFA score) ranges from 0 (normal patient) to 24 (most severe patient). Vincent JL, de Mendonça A, Cantraine F, et al. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on "sepsis-related problems" of the European Society of Intensive Care Medicine. Crit Care Med. 1998;26(11):1793-800.
Time frame: 48 hours
Change in SOFA 72
Differences between SOFA score at inclusion (SOFA0) and SOFA score at 72 hours. The sequential organ failure assessment score (SOFA score) ranges from 0 (normal patient) to 24 (most severe patient). Vincent JL, de Mendonça A, Cantraine F, et al. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on "sepsis-related problems" of the European Society of Intensive Care Medicine. Crit Care Med. 1998;26(11):1793-800.
Time frame: 72 hours
Change in SOFA 7d
Differences between SOFA score at inclusion (SOFA0) and SOFA score at day 7. The sequential organ failure assessment score (SOFA score) ranges from 0 (normal patient) to 24 (most severe patient). Vincent JL, de Mendonça A, Cantraine F, et al. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on "sepsis-related problems" of the European Society of Intensive Care Medicine. Crit Care Med. 1998;26(11):1793-800.
Time frame: 7 days
ventilator free days
ventilator free days (VFDs) are defined as follows: VFDs=0: If the patient dies before 28 days. VFDs=(28-x): If the patient is success-fully weaned from mechanical ventilation within 28 days, where x is the number of days spent receiving mechanical ventilation. VFDs=0: If the patient requires mechanical ventilation for 28 days or more.
Time frame: 28 days
vasopressor free days
vasopressor free days (VaFDs) are defined as follows: VaFDs=0: If the patient dies before 28 days. VaFDs=(28-x): If the patient is successfully weaned from vasopressor within 28 days, where x is the number of days spent with vasopressor. VaFDs=0: If the patient requires vasopressor for 28 days or more.
Time frame: 28 days
renal replacement therapy free days
renal replacement therapy free days (RRFDs) are defined as follows: RRFDs=0: If the patient dies before 28 days. RRFDs=(28-x): If the patient is successfully weaned from renal replacement therapy within 28 days, where x is the number of days spent with vasopressor. RRFDs=0: If the patient requires renal replacement therapy for 28 days or more.
Time frame: 28 days
ICU length of stay
time spent in ICU from inclusion censored at 28 days
Time frame: 28 days
Ischemic
Incidence of ischemic event during the first 28 days (stroke, myocardial infarction, mesenteric infarction)
Time frame: 28 days
thrombosis
Incidence of deep venous thrombosis or pulmonary embolism during the first 28 days
Time frame: 28 days
TRIALI
Incidence of transfusion-related acute lung injury during the first 28 days
Time frame: 28 days
Transfusion reaction
Incidence of side effects of transfusions during the first 28 days (fever, chills, hemolysis)
Time frame: 28 days
Plan to share: Undecided
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Ran from Mar 2019 to primary completion in Feb 2024, 59 months.
Of 39 non-industry phase 3 interventional studies under Shock, Septic, half reached primary completion within 42 months of starting (the median), counting those still running; a quarter within 17 and three quarters within 59. This study's 59 months is above that.
Counting every sponsor, half of 40 studies reached it within 42 months; a quarter within 17 and three quarters within 59.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Jun 2024. You cannot join it, but the record below documents what was studied.
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