Platelet Transfusion in Critically Ill Patients With Thrombocytopenia (TRAMPOLINE)

Thrombocytopenia is a common biological disorder in critically ill patients. The main supportive treatment is platelet transfusion with the aim of preventing and treating bleeding and securing invasive procedures. Current guidelines suggest that prophylactic platelet transfusion should probably be administered in non-bleeding critically ill patients at platelet count triggers of 10 to 20 G/L, albeit with very low certainty since extrapolated from studies carried out in stable patients with hematological malignancies. Indications for prophylactic platelet transfusion have not been properly addressed in adult ICU patients with regard to their particular risk of bleeding and prognosis. We propose the TRAMPOLINE study in order to address two different platelet count thresholds of 10 G/L (low threshold) or 20 G/L (high threshold) for the prevention of ICU-acquired bleeding in critically ill patients with severe thrombocytopenia.

Study Overview

• Status: Not yet recruiting
• Conditions: Thrombocythemia
• Intervention / Treatment: Other: Platelet transfusion if platelet count ≤ 10 G/L; Other: Platelet transfusion when platelet count ≤ 20 G/L

• Study Type: Interventional
• Enrollment (Estimated): 536
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Frédéric Pene, MD PhD; Phone Number: +33 0158414677; Email: frederic.pene@aphp.fr
• Study Contact Backup: Name: Jérôme Lambert, MD PhD; Phone Number: +33 0142499742; Email: jerome.lambert@u-paris.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 y.o. AND

2. Hospitalisation in the ICU with at least one of the following life support during the current ICU stay (past or ongoing, regardless of indications)

   • circulatory support (inotropes/ vasopressors at any dose)
   • respiratory support (invasive mechanical ventilation, non-invasive ventilation, continuous positive airway pressure (CPAP), high-flow nasal oxygen, O2 supply ≥ 6 L/min)
   • renal replacement therapy for metabolic disturbances and/or acute and acute-on chronic kidney failure (if not previously under chronic hemodialysis) AND
3. Platelet count ≤ 20 G/L within the last 24h (first occurrence at any time during the ICU stay) AND
4. expected ICU stay for at least 48 hours from the time of enrollment AND
5. Signed consent by the patient or his/her relative, or under an emergency procedure (emergency enrollment notified in the medical file, with requirement for confirmation consent a posteriori)

Exclusion Criteria:

1. Major bleeding (WHO grade 3-4) or mild bleeding (WHO grade 2) within the present hospitalization
2. Major surgery within the recent 72 hours
3. Intracranial or retinal bleeding within the recent 7 days
4. Non- or contra-indication to prophylactic platelet transfusion (immune thrombocytopenia, thrombotic microangiopathy)
5. Indications for increased prophylactic platelet transfusion threshold > 20 G/L (conditions associated with increased risk of bleeding including, but not limited to extra-corporeal membrane oxygenation, therapeutic anticoagulant treatment, fibrinolysis…)
6. Known full refractory status to platelet transfusion (prophylactic transfusion not recommended)
7. Prophylactic platelet transfusion already applied at platelet count ≤ 20 G/L during the present ICU stay
8. Patient opposed to transfusion of blood products
9. Moribund patients (death expected within the next 24 hours)
10. Pregnancy/breastfeeding
11. Not covered by French Social Security (health insurance)
12. Patient under safeguarding of justice

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Low-threshold	Other: Platelet transfusion if platelet count ≤ 10 G/L; Platelet transfusion as soon as platelet count falls ≤ 10 G/L
Experimental: High threshold	Other: Platelet transfusion when platelet count ≤ 20 G/L; Platelet transfusion will be initiated immediately after randomisation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of ICU-acquired severe and debilitating bleeding	Grades 3-4 of the modified WHO bleeding scale, assessed during the ICU stay, from the time of randomization to ICU discharge (or to the end of 28-day intervention period in patients remaining in the ICU after 28 days). Bleeding events will be collected up to 72h after ICU discharge. The modified WHO bleeding scale, commonly used in observational studies and trials to assess the severity of bleeding. It comprises 4 grades: grade 1 (minor blood loss), grade 2 (mild blood loss), grade 3 (severe blood loss (most often requiring Red Blood Cell transfusion) and grade 4 (debilitating blood loss).	Until ICU discharge or up to 28 days in ICU

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of ICU-acquired mild bleeding	WHO grade 2	Until ICU discharge or at 28 days in ICU
Incidence of ICU-acquired mild to debilitating bleeding	WHO grade 2-3-4	Until ICU discharge or up to 28 days in ICU
Total number of platelet transfusions episodes		Until ICU discharge or up to 28 days in ICU
Number of prophylactic platelet transfusions episodes		Until ICU discharge or up to 28 days in ICU
Doses of transfused platelets		Until ICU discharge or up to 28 days in ICU
Number of packed red cell transfusions		Until ICU discharge or up to 28 days in ICU
Volumes of packed red cell transfusions		Until ICU discharge or up to 28 days in ICU
Volumes of fresh frozen plasma		Until ICU discharge or up to 28 days in ICU
Incidence of ICU-acquired infections		Up to 72 hours after ICU discharge
Incidence of acquired arterial thrombotic events	Acute coronary syndrome, acute limb ischemia, mesenteric ischemia, stroke	Up to 72 hours after ICU discharge
Incidence of acquired venous thrombotic events	Thrombophlebitis and pulmonary embolism	Up to 72 hours after ICU discharge
Incidence of Central Venous Catheter (CVC)-related hemorrhagic and infectious complications		Up to 72 hours after ICU discharge
Incidence of platelet transfusion-related side effects	Any significant transfusion reaction such as chills and fever or side effect requiring to be reported to the local hemovigilance system	Up to 72 hours after ICU discharge
Incidence of transfusion-related pulmonary manifestations (acute pulmonary oedema and acute lung injury (TRALI))		Up to 72 hours after ICU discharge
Incidence of anti-HLA/HPA immunization	Investigated in case of platelet transfusion refractoriness	Up to 72 hours after ICU discharge
In ICU survival	Investigated in case of platelet transfusion refractoriness	Up to 90 days
In hospital survival	Investigated in case of platelet transfusion refractoriness	Up to 90 days
28 day survival	Investigated in case of platelet transfusion refractoriness	At 28 days
In ICU length of stay		Up to 90 days
In hospital length of stay		Up to 90 days
90-day survival		Up to 90 days
90-day hospital costs	From randomization to day 90	Up to 90 days

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2024
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2028

Study Registration Dates

• First Submitted: September 13, 2024
• First Submitted That Met QC Criteria: September 13, 2024
• First Posted (Estimated): September 19, 2024

Study Record Updates

• Last Update Posted (Estimated): September 19, 2024
• Last Update Submitted That Met QC Criteria: September 13, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Thrombocythemia; Platelet transfusion
• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Blood Platelet Disorders; Cytopenia; Thrombocytosis; Thrombocytopenia
• Other Study ID Numbers: APHP230835

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No