TRANSfusion in Patients With Onco-hematological Malignancies ResusciTated From Septic Shock
- Conditions
- Septic ShockCancerAnemia
- Interventions
- Biological: Restrictive Red blood cell transfusionBiological: Liberal Red blood cell transfusion
- Registration Number
- NCT03837171
- Lead Sponsor
- Assistance Publique - Hôpitaux de Paris
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 192
- Age > 18 years
- Evolutive (complete remission < 2 years) malignant solid tumor or chronic or acute hematological malignancy
- Septic shock defined as:
- Presumed or documented infection
- Acute circulatory failure defined as hypotension requirement of vasoactive drugs for more than one hour (norepinephrine or epinephrine ≥ 0.1 µg/kg/min)
- Tissue hypoxia defined by arterial lactate level > 2 mmol/L within 3 hours prior to inclusion
- Hemoglobin level < 9 g/dL
- Informed consent from patients or surrogates
- Acute life-threatening bleeding
- Ongoing acute coronary syndrome or any other acute ischemic condition
- End-of-life decisions at the time of ICU admission
- Refusal of transfusions for personal beliefs
- Lack of social security coverage
- Pregnancy or breastfeeding
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Restrictive strategy Restrictive Red blood cell transfusion Maintain a hemoglobin level \> 7 g/dL during the resuscitation of septic shock Liberal strategy Liberal Red blood cell transfusion Maintain a hemoglobin level \> 9 g/dL during the first 48 hours of resuscitation of septic shock
- Primary Outcome Measures
Name Time Method Tissue oxygenation 12 hours 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
- Secondary Outcome Measures
Name Time Method Tissue oxygenation 24 24 hours 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 24hMortality 7 7 days Percentage of Death at 7 days
Mortality 28 28 days Percentage of Death at 28 days
ICU length of stay 28 days time spent in ICU from inclusion censored at 28 days
Ischemic 28 days Incidence of ischemic event during the first 28 days (stroke, myocardial infarction, mesenteric infarction)
Change in SOFA 7d 7 days 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.Tissue oxygenation 6 6 hours 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 6hICU mortality 28 days Percentage of Death in ICU at 28 days
Hospital mortality 28 days Percentage of Death in Hospital at 28 days
renal replacement therapy free days 28 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.Tissue oxygenation 48 48 hours 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 48hChange in SOFA 48 48 hours 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.Change in SOFA 24 24 hours 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.Change in SOFA 72 72 hours 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.ventilator free days 28 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.Transfusion reaction 28 days Incidence of side effects of transfusions during the first 28 days (fever, chills, hemolysis)
vasopressor free days 28 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.thrombosis 28 days Incidence of deep venous thrombosis or pulmonary embolism during the first 28 days
TRIALI 28 days Incidence of transfusion-related acute lung injury during the first 28 days
Trial Locations
- Locations (20)
GH Édouard Herriot
🇫🇷Lyon, France
CHU Amiens Picardie Site Sud
🇫🇷Amiens, France
Hopital Robert Ballanger
🇫🇷Aulnay-sous-Bois, France
Hopital Avicenne AP-HP
🇫🇷Bobigny, France
Salengro, CHRU
🇫🇷Lille, France
CH sud-Francilien
🇫🇷Corbeil, France
Hopital Henri Mondor AP-HP
🇫🇷Créteil, France
CH Lyon Sud
🇫🇷Lyon, France
CHV André Mignot
🇫🇷Le Chesnay, France
La Source, CHR
🇫🇷Orléans, France
Institut Paoli Calmettes
🇫🇷Marseille, France
GH Sud Ile de France
🇫🇷Melun, France
Bel Air CHR
🇫🇷Metz, France
CHU de Nantes
🇫🇷Nantes, France
Mercy, CHR
🇫🇷Metz, France
Hopital Cochin AP-HP
🇫🇷Paris, France
Hopital de La Pitié Salpetriere AP-HP
🇫🇷Paris, France
Hopital Saint Louis AP-HP
🇫🇷Paris, France
Hopital Saint Antoine AP-HP
🇫🇷Paris, France
Gustave Roussy
🇫🇷Villejuif, France