Preoperative use of Romiplostim in thrombocytopenic patients undergoing cardiac surgery. A Phase 3, multicenter randomized double-blinded controlled against placebo study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Nantes

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Analytical,Diagnostic,Therapeutic Techniques and Equipment [E]-Surgical Procedures, Operative [E04]

Decision date (initial)

2025-10-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To determine the efficacy of a platelet growth factor (Romiplostim) administered preoperatively in thrombocytopenic patients on the severity of thrombocytopenia after cardiac surgery compared with placebo.

Secondary objectives 4

1. To determine the impact of a platelet growth factor (Romiplostim) administered preoperatively compared with placebo on blood transfusion in the operating room and in the first 28 days postoperatively
2. To determine the impact of a platelet growth factor (Romiplostim) administered pre-operatively compared to Placebo on the evolution of blood count (CBC) parameters since injection and in the first 28 days post-operatively.
3. To determine the impact of a platelet growth factor (Romiplostim) administered pre-operatively compared to Placebo on intra- and post-operative bleeding volume at D+1.
4. To determine the impact of a platelet growth factor (Romiplostim) administered preoperatively compared with placebo on intraoperative and postoperative morbidity and mortality.

Conditions and MedDRA coding

thrombocytopenic patients undergoing cardiac surgery

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Adult patients with no upper age limit
2. Programmed cardiac surgery with ECC
3. Patient with pre-operative thrombocytopenia strictly <150,000/mm3
4. Surgery performed with a centrifugal blood recovery system (Cell Saver type) or equivalent
5. Feasibility of a 1st injection (Romiplostim or Placebo) between D-14 and D-10 before surgery
6. Surgery requiring a minimum of 1 month post-operative antiaggregant and/or anticoagulant treatment

Exclusion criteria 28

1. Inability to perform the first injection of Romiplostim or Placebo within 10 days prior to surgery
2. Cardiac surgery without extracorporeal circulation
3. Patients who do not speak French
4. Patient without Social Security
5. Known hereditary or acquired thrombophilia, with or without a history of thrombosis
6. History of ischemic or hemorrhagic stroke
7. History of phlebitis, pulmonary embolism or portal thrombosis
8. Myelogram in favor of hematologic malignancy or blasts strictly greater than 5%
9. Malignant pathologies with last follow-up in favor of disease progression
10. Coronary artery bypass graft surgery due to one or more significant coronary stenoses
11. 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
12. Severe chronic liver disease with CHILD-PUGH score > 6 (measured without decompensation)
13. Intended use of aprotinin as an antifibrinolytic agent during surgery
14. Patient with contraindication to discontinuing all antiplatelet therapy prior to surgery (with discontinuation of at least 3 days for acetylsalicylic acid and at least 5 days for clopidogrel/ticagrelor)
15. History of heart attack with stent placement less than one year ago
16. Immobilization of a limb (e.g., plaster cast for a broken ankle) or inability to walk independently due to motor impairment (e.g., complete paralysis of a limb) or medical contraindication (e.g., strict bed rest required)
17. Treatment with thrombopoietin receptor agonists received within 3 months prior to inclusion
18. Current 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
19. Hypersensitivity to Romiplostim or any of its excipients, or to proteins derived from E. coli.
20. Context of hyperchloremia, hypernatremia, or major water and sodium retention with anasarca refractory to medical treatment
21. Treatment with JAK2 inhibitor in progress or less than 1 month old
22. Known hemophilia
23. Pregnant woman or woman of childbearing age not using effective contraception
24. Current contraception with estrogen-progestin pill or estrogen-containing oral hormone replacement therapy
25. Nursing mother
26. Minor
27. Major under guardianship, curatorship or safeguard of justice
28. Treatment with Rituximab within the last 7.5 months or intravenous immunoglobulin within the last 40 days

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Lowest platelet count measured between the end of CEC and the 7th postoperative day with D0 = day of surgery. This criterion will take into account any tests performed at the hospital or in the city (if the patient is discharged from the hospital before the 7th postoperative day).

Secondary endpoints 9

1. Transfusion of platelet concentrate (PC) (yes/no and number) - Per-operatively up to 24th hour, per-operatively up to 7th day, per-operatively up to 28th day
2. Transfusion of red blood cell concentrate (RGC) (yes/no and number) - Per-operatively up to 24th hour, per-operatively up to 7th day, per-operatively up to 28th day
3. Transfusion of fresh frozen plasma (FFP) (yes/no and number) - Per-operatively up to 24th hour, per-operatively up to 7th day, per-operatively up to 28th day
4. Administration of blood-derived drugs: fibrinogen, prothrombin complex concentrates, recombinant activated factor VII - Per-operatively up to 24th hour, per-operatively up to 7th day, per-operatively up to 28th day
5. Lowest platelet count in the first 28 days post-operatively
6. Highest platelet count in the first 7 days and in the first 28 days post-operatively
7. Lowest haemoglobin in the first 7 days and in the first 28 days post-operatively
8. Post-operative bleeding volume: - From sternal closure to 12th post-operative hour, - From discharge to 24th post-operative hour - From the 24th postoperative hour to drain removal, - Classification of bleeding according to UDPB classes,65 - Surgical revision (including sternal reopening), - Intraoperative blood recovery (volume treated and volume restored).
9. Postoperative morbidity and mortality: - Intraoperative and 24h bleeding/hemorrhagic events - Duration of mechanical ventilation in intensive care unit (in hours), - Bleeding event within 3 months post-op: - Venous and arterial thromboembolic events within 3 months post-operatively - Infection within 3 months : - Organ dysfunction, - Length of stay in intensive care unit, - Length of hospital stay, - Mortality at D28 post-op.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Nantes

Sponsor organisation

Centre Hospitalier Universitaire De Nantes

Address

5 Allee De L Ile Gloriette, Cs 69301 Cs 69301

City

Nantes Cedex 1

Postcode

44093

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Nantes

Contact name

Dr Jean-Christophe RIGAL

Public contact point

Organisation

Centre Hospitalier Universitaire De Nantes

Contact name

Dr Jean-Christophe RIGAL

Locations

1 EU/EEA country · 8 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications