Symptoms and General Pathology

All Conditions

Blood and Lymph Conditions

Neoplasms

Infections

Shock

Anemia

Hematologic Neoplasms

Shock, Septic

Hematologic Diseases

Sepsis

Toxemia

Communicable Diseases

Syndrome

Systemic Inflammatory Response Syndrome

Inflammation

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

All Drugs and Chemicals

Central Nervous System Depressants

Other Dietary Supplements

Chrysarobin

Benzocaine

Tannic Acid

Maintain a hemoglobin level \> 9 g/dL during the first 48 hours of resuscitation of septic shock

Maintain a hemoglobin level \> 7 g/dL during the resuscitation of septic shock

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

Liberal Red blood cell transfusion

Hemoglobin level will be maintained above 7 g/dL (restrictive strategy) during all the stay in ICU

Restrictive Red blood cell transfusion

Frederic PENE, MD, PhD

Matthieu RESCHE-RIGON, MD PhD

frederic PENE, MD

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.

TRANSfusion in Patients With Onco-hematological Malignancies ResusciTated From Septic Shock

Stratégie Transfusionnelle érythrocytaire Dans la réanimation du Choc Septique du Patient d'Onco-hématologie : Essai randomisé Multicentrique TRANSPORT [TRANSfusion in Patients With Onco-hematological Malignancies ResusciTated From Septic Shock]

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

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

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

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

Percentage of Death in Hospital at 28 days

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.

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.

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.

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.

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.

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.

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 spent in ICU from inclusion censored at 28 days

Incidence of ischemic event during the first 28 days (stroke, myocardial infarction, mesenteric infarction)

Incidence of deep venous thrombosis or pulmonary embolism during the first 28 days

Incidence of transfusion-related acute lung injury during the first 28 days

Incidence of side effects of transfusions during the first 28 days (fever, chills, hemolysis)

Assistance Publique - Hôpitaux de Paris

Digestive System Diseases

Gland and Hormone Related Diseases

Behaviors and Mental Disorders

Rare Diseases

Stomach Neoplasms

Fatigue

Pancreatic Neoplasms

Quality of Life

Stomach Cancer

Pancreatic Cancer

Hematinics

Epoetin Alfa

Patients enrolled in the study will be randomized to receive either 40,000 units of epoetin alfa on day 1 and day 8. Hemoglobin, hematocrit, reticulocyte count, reticulocyte hemoglobin, and immature reticulocyte count will be measured on days 1, 4, 8, and once between post-operative days 20 and 30. Pre-operatively and between post-operative days 20 and 30 patients will complete a quality of live assessment tool (FACT-An) to assess their fatigue related to anemia.

Patients enrolled in the study will be randomized to receive either 40,000 units of placebo (saline) on day 1 and day 8. Hemoglobin, hematocrit, reticulocyte count, reticulocyte hemoglobin, and immature reticulocyte count will be measured on days 1, 4, 8, and once between post-operative days 20 and 30. Pre-operatively and between post-operative days 20 and 30 patients will complete a quality of live assessment tool (FACT-An) to assess their fatigue related to anemia.

Epoetin Alfa group

Placebo group

Stephen R. Grobmyer, MD

This pilot study is looking at how well epoetin alfa, given in the immediate post-operative period, works in reducing anemia and the need for transfusions.

This is a pilot, single center, prospective, double blinded, randomized study comparing epoetin alfa versus placebo. Eligible patients will just have undergone a major abdominal operation for malignancy (esophagectomy, gastrectomy, partial hepatectomy, partial pancreatectomy, or low anterior resection of rectum) and have a post-operative hemoglobin greater than 8 g/dL and less than 11 g/dL on post-operative day #1. On post-operative day #1 patients enrolled in the study will be randomized to receive either 40,000 units of epoetin alfa or placebo. On post-operative day #8, the patients will receive an additional dose of epoetin alfa or placebo (depending on randomization assignment and Hgb level). Hemoglobin, hematocrit, reticulocyte count, reticulocyte hemoglobin, and immature reticulocyte count will be measured on days 1, 4, 8, and once between post-operative days 20 and 30. Pre-operatively and between post-operative days 20 and 30 patients will complete a quality of live assessment tool (FACT-An) to assess their fatigue related to anemia.

Pilot Study of Epoetin Alfa for Patients Having Abdominal or Pelvic Surgery for Cancer

Placebo-Controlled Pilot Study to Assess the Post-Operative Administration of Epoetin Alfa on Patients Undergoing Abdominal or Pelvic Surgery for Malignancy

Ortho Biotech Clinical Affairs, L.L.C.

University of Florida

Preleukemia

Myelodysplastic Syndromes

Bone Marrow Diseases

Precancerous Conditions

Antineoplastic Agents

ON 01910

Protein Kinase Inhibitors

Enzyme Inhibitors

Patients will take 560 mg oral rigosertib (two 280 mg capsules) in the morning and 280 mg (one 280 mg capsule) in the afternoon, in fasting conditions, for 21 consecutive days of 21-day cycle (continuous regimen).

Dose of 560 mg consists of two (2) 280 mg soft gel capsules of rigosertib.

Oral rigosertib

Steven M. Fruchtman, MD

The study will enroll low risk MDS patients who need red blood cell transfusions and who are refractory to or are not using erythropoiesis-stimulating agents. The purpose of the study is to determine whether oral rigosertib treatment results in hematological improvements according to the 2006 International Working Group criteria in these patients. The study will also record any side effects that may occur during the study.

This will be a Phase II, single-arm, multicenter study (approximately 15 centers). Approximately 40 transfusion-dependent patients with Low- or Int-1 risk Myelodysplastic Syndrome (MDS) by International Prognostic Scoring System (IPSS) will be enrolled and treated with oral rigosertib administered twice daily for 21 consecutive days of a 21-day cycle (continuous regimen) in order to obtain at least 35 evaluable patients treated for at least 8 weeks. Patients will take 560 mg rigosertib (two 280 mg capsules) in the morning and 280 mg (one 280 mg capsule) in the afternoon, in fasting conditions. All patients on intermittent regimen at the time of Amendment 2 of the Protocol will be switched to the continuous regimen, including patients on reduced doses.

Oral Rigosertib in Low Risk MDS Patients Refractory to ESAs

A Single-arm Study to Assess the Efficacy and Safety of Oral Rigosertib in Transfusion-dependent, Low or Intermediate-1, Myelodysplastic Syndrome Patients Based on the International Prognostic Scoring System

The number of patients who achieve hematologic improvement will be documented. Hematologic improvement is defined by the 2006 International Working Group (IWG) response criteria for the erythroid, platelet and neutrophil lineages.

The number of patients with a complete remission or a partial remission will be documented. Complete remission and partial remission are defined according to 2006 IWG response criteria for MDS. Overall response = complete remission + partial remission.

The number of weeks a complete remission or a partial remission is observed in a patient will be documented.

Specific safety parameters and procedures will include recording of medical history, medication history, physical examination, measurement of vital signs (blood pressure, temperature, respiration rate, and pulse), weight, laboratory evaluations, and toxicity and AE assessments.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
TRANSfusion in Patients With Onco-hematological Malignancies ResusciTated From Septic Shock	NCT03837171	Septic Shock Anemia Cancer	Liberal Red blo... Restrictive Red...	18 Years -	Assistance Publique - Hôpitaux de Paris
Pilot Study of Epoetin Alfa for Patients Having Abdominal or Pelvic Surgery for Cancer	NCT00294203	Anemia	Epoetin Alfa gr... Placebo group	18 Years -	University of Florida
Pilot Study of Epoetin Alfa for Patients Having Abdominal or Pelvic Surgery for Cancer	NCT00294203	Anemia	Epoetin Alfa gr... Placebo group	18 Years -	University of Florida
Oral Rigosertib in Low Risk MDS Patients Refractory to ESAs	NCT01904682	Myelodysplastic...	Oral rigosertib	18 Years -	Traws Pharma, Inc.

Spots Global Cancer Trial Database for erythrocyte transfusion