Preoperative Use of Romiplostim in Thrombocytopenic Patients Undergoing Cardiac Surgery.

Official title

Preoperative Use of Romiplostim in Thrombocytopenic Patients Undergoing Cardiac Surgery. A Phase 3, Multicenter Randomized Double-blinded Controlled Against Placebo Study.

Overview

Romiplostim has demonstrated its efficacy and good tolerance in multiple indications. If the efficacy of Romiplostim is confirmed in this population, thrombocytopenic patients will be able to undergo cardiac surgery, which is generally life-saving, without prior thrombocytopenia. Patients included in the study will be hospitalized within 15 days of the first administration of the study treatment and will be closely monitored clinically and biologically for at least 10 days after surgery. The occurrence of an adverse event can therefore be quickly detected and managed. Collectively, "Patient Blood Management" strategies are mainly focused on the management of preoperative anemia. If positive, this study will enrich the therapeutic arsenal available for optimizing patients in preparation for major surgery. As no major collective complications are expected, the collective benefit/risk ratio also appears favorable.

Interventions

• Drug Nplate
  The dosage for this first injection will be: * 2 µg/kg for patients with a platelet count at inclusion between 149,000 and 100,000/mm3 * 3 µg/kg for patients with a platelet count strictly below 100,000/mm3
• Drug NaCl %0.9
  NaCl (Sodium chloride) 0.9% administered subcutaneously

Primary outcome measures

• Efficacy [Time frame: Day 7]

Secondary outcome measures (12)

• Transfusion of platelet concentrate [Time frame: Day 1]
• Transfusion of platelet concentrate [Time frame: Day 7]
• Transfusion of platelet concentrate [Time frame: Day 28]
• Transfusion of red blood cell concentrate [Time frame: Day 1]
• Transfusion of red blood cell concentrate [Time frame: Day 7]
• Transfusion of red blood cell concentrate [Time frame: Day 28]
• Transfusion of fresh frozen plasma [Time frame: Day 1]
• Transfusion of fresh frozen plasma [Time frame: Day 7]
• Administration of blood-derived drugs [Time frame: Day 1]
• Administration of blood-derived drugs [Time frame: Day 7]
• Administration of blood-derived drugs [Time frame: Day 28]
• Efficacy [Time frame: Day 28]

Eligibility criteria

Inclusion criteria

• Adult patients with no upper age limit,
• Scheduled cardiac surgery with cardiopulmonary bypass,
• Patients with preoperative thrombocytopenia strictly <150,000/mm3
• Surgery performed with a blood recovery system using centrifugation (Cell Saver type) or equivalent,
• Feasibility of a first injection (Romiplostim or Placebo) between D-14 and D-10 before surgery,
• Surgery requiring the administration of antiplatelet and/or anticoagulant therapy for a minimum of 1 month postoperatively.

Exclusion criteria

• Inability to administer the first injection of Romiplostim or Placebo within 10 days prior to surgery,
• Cardiac surgery without cardiopulmonary bypass,
• Coronary artery bypass graft surgery due to one or more significant coronary stenoses presenting with unstable angina (defined by anginal pain at rest, or with minimal exertion, or pain that has recently worsened),
• Tangential filtration blood recovery system (i-SEP SAME® type) planned for intraoperative use or absence of intraoperative blood recovery system due to investigator choice or availability issues,
• Planned use of aprotinin as an antifibrinolytic agent during surgery,
• Patients treated with clopidogrel (Plavix) or ticagrelor who cannot switch to acetylsalicylic acid (Kardégic) monotherapy at least 5 days before surgery. The study allows for continued use of acetylsalicylic acid (Kardégic) as well as anticoagulants,
• Hereditary or acquired thrombophilia with or without a history of thrombosis,
• History of ischemic or hemorrhagic stroke,
• History of phlebitis, pulmonary embolism, or portal vein thrombosis,
• History of myocardial infarction with coronary stenting that occurred less than one year ago,
• Current limb immobilization (e.g., plaster cast for ankle fracture) or inability to walk independently due to limited mobility (e.g., paralysis),
• Current immobilization of a limb (e.g., plaster cast for ankle fracture) or inability to walk independently due to motor limitation (e.g., complete paralysis of a limb) or medical contraindication (e.g., strict bed rest required),
• Myelogram indicating malignant hematological disease or blast cells strictly greater than 5%,
• Malignant diseases with last follow-up indicating disease progression,
• Severe chronic liver disease with a CHILD-PUGH score > 6 or B (measured without decompensation),
• Treatment with thrombopoietin receptor agonist received within 3 months prior to inclusion,
• Treatment with JAK2 inhibitor currently underway or within the last month,
• Treatment with Rituximab within the last 7.5 months or intravenous immunoglobulin within the last 40 days,
• Ongoing treatment with corticosteroids at doses equal to or greater than 20mg of hydrocortisone, 5mg of prednisone/or prednisolone, 4mg of methylprednisone, or 0.75mg of dexamethasone,
• Known hemophilia,
• Hypersensitivity to romiplostim or any of its excipients, or to proteins derived from E. coli,
• Context of hyperchloremia, hypernatremia, or major water and salt retention with anasarca refractory to medical treatment,
• Pregnant women or women of childbearing age who are not using effective contraception,
• Currently using combined oral contraceptive pills or oral hormone replacement therapy containing estrogen,
• Breastfeeding women,
• Minors,
• Adults under guardianship, curatorship, or judicial protection,
• Patients who do not speak French,
• Patients without Social Security coverage.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

France · 8 centers

• CHU d'Angers — Angers
• CHU de Bordeaux — Bordeaux
• CHU de Brest — Brest
• CHU de Dijon — Dijon
• CHU de Nantes — Nantes
• Hôpital Bichat (AP-HP) — Paris
• CHU de Rennes — Rennes
• CHU de Strasbourg — Strasbourg

Identifiers

NCT: NCT07278661 · RC24_0458 · 2024-517710-15-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗