Perioperative Eltrombopag in Patients With Inherited Thrombocytopenia

NCT03638817 | Completed Phase 2 DMC

• 2 other identifiers: RC31/16/89132017-004489-88
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 25

Brief Summary

The objective of the study is to estimate the response to eltrombopag based on platelet count increase above a safety level of 80 G/L and lack of requirement for pre-, per- and post-operative administration of platelet concentrates (PC) for performing elective invasive acts at mild or high bleeding risk,in selected patients with inherited thrombocytopenia (IT).

Conditions

Thrombocytopenia

Keywords

Inherited thrombocytopenias (IT); Platelet concentrates (PC); Eltrombopag; Surgery; Invasive acts; Perioperative; Rare disease; Thrombopoietin mimetic

Outcome Measures

Primary Outcomes (1)

• Perioperative management by eltrombopag in inherited thrombocytopenia

  The response to Eltrombopag is a composite criteria including the level of platelet count 2 days before the procedure and the requirement of PC administration at any time in the study period. The "study period" is running from the start of treatment (inclusion visit) to 4 weeks after completion of treatment. A platelet count remaining below 80 G/L preoperatively, whether or not eltrombopag was taken, is a criterion of failure of treatment.

  up to 4 weeks after completion of treatment

Secondary Outcomes (7)

• Adverse events

  up to 4 weeks after completion of treatment

• Excessive bleeding

  up to 4 weeks after completion of treatment

• Vascular thrombosis

  up to 4 weeks after completion of treatment

• Doses of eltrombopag on-treatment

  2 and 4 weeks after the beginning of the treatment

• Platelet kinetics

  up to 4 weeks after completion of treatment

Study Arms (1)

Eltrombopag

EXPERIMENTAL

Drug: Eltrombopag

Interventions

Eltrombopag DRUG

Eltrombopag will be prescribed at doses recommended in primary immune thrombocytopenia (50, 25 or 75 mg), starting 4 weeks before the procedure and stopped 2 days before. PC will be administrated prophylactically if the platelet count is \< 80 G/L or per/post-operatively in case of bleeding of undetermined cause. Antifibrinolytics will be authorized and low molecular weight heparin prescribed if indicated for the prophylaxis of postoperative venous thrombosis according to the standard dose and duration, , irrespective of the platelet count

Eltrombopag

Eligibility Criteria

• Age: 6 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Symptomatic patients with bleeding history and chronic thrombocytopenia with strong presumption of constitutional origin on the basis of
• the identified mutation and/or
• a combination of the following criteria: familial antecedent with Mendelian transmission, duration of thrombocytopenia, suggestive syndromic presentation, and evidence against primary or secondary immune thrombocytopenia, especially absence of immunologic markers and failure of previous conventional or immunosuppressive therapies.
• Averaged platelet counts during the last five years below the safety level required for the procedure.
• Scheduled (\>4 weeks) surgery or invasive procedure with anticipated risk of bleeding: e.g. needle biopsy of solid organ (liver, kidney….etc.), interventional endoscopy, major surgeries, or surgery without possibility of mechanical control of haemostasis (e.g. tonsillectomy). Written informed consent of the patient or his (her) parents or tutors (patients \< 18 yrs).
• Patients included in the French national registry of rare platelet disorders
• Patient with social insurance coverage

You may not qualify if:

• questionable constitutional origin;
• definite platelet dysfunction associated to thrombocytopenia (eg: gray platelet syndrome, NBEAL2 and related gene mutations, homozygous Bernard-Soulier Syndrome);
• thrombocytopenia with predisposition to hematologic malignancies (e.g; RUNX1, ETV6 or ANKRD26 gene mutations).
• amegakaryocytic thrombocytopenia resulting from mutations in the thrombopoietin (TPO) TPO-Mpl receptor, supposed, by definition, to be hardly responsive to receptor agonists.
• questionable requirement of prophylactic PC transfusions;
• procedure usually associated with platelet consumption requiring transfusions of PC (e.g.: cardiac surgery), making difficult the evaluation of success or failure;
• procedures at risk of bleeding with immediate vital or functional consequences (e.g.: intra cranial surgery);
• personal history of arterial or venous thromboembolic events or known familial thrombophilia;
• association with another acquired or constitutional hemorrhagic diathesis;
• chronic hepatitis, cirrhosis, with moderate to severe liver failure (Child-Pugh score ≥5);
• previous or concurrent myeloid malignancy, including myelodysplastic syndrome;
• alanine aminotransferase (ALT) or bilirubin levels 2 times the upper limit of normal (ULN);
• altered renal function (creatinin clearance \<30 ml/min);
• refusal of safe contraception;
• ocular lenses opacity;

Sponsors & Collaborators

• University Hospital, Toulouse: lead
• French network for inherited hemorragic diseases: collaborator
• National Reference Centre for Platelet Pathologies: collaborator

Study Sites (25)

Angers Hospital

Angers, France

Location

Bensancon Hospital

Besançon, France

Location

Bordeaux Hospital

Bordeaux, France

Location

Caen Hospital

Caen, France

Location

Clermont-Ferrand Hospital

Clermont-Ferrand, France

Location

Dijon Hospital

Dijon, France

Location

Lille Hospital

Lille, France

Location

Hospices Civils Lyon

Lyon, France

Location

Marseille Hospital

Marseille, France

Location

Montpellier Hospital

Montpellier, France

Location

Nancy Hospital

Nancy, France

Location

Nantes Hospital

Nantes, France

Location

Cochin Hospital

Paris, France

Location

Hopital Europeen G Pompidou

Paris, France

Location

Kremlin Bicetre Hospital

Paris, France

Location

Necker Hospital

Paris, France

Location

Robert Debré Hospital

Paris, France

Location

Trousseau Hospital

Paris, France

Location

Poitiers Hospital

Poitiers, France

Location

Reims Hospital

Reims, France

Location

Rennes Hospital

Rennes, France

Location

Rouen Hospital

Rouen, France

Location

Strasbourg Hospital

Strasbourg, France

Location

university hospital Toulouse

Toulouse, France

Location

Tours Hospital

Tours, France

Location

Related Publications (7)

• Pecci A, Gresele P, Klersy C, Savoia A, Noris P, Fierro T, Bozzi V, Mezzasoma AM, Melazzini F, Balduini CL. Eltrombopag for the treatment of the inherited thrombocytopenia deriving from MYH9 mutations. Blood. 2010 Dec 23;116(26):5832-7. doi: 10.1182/blood-2010-08-304725. Epub 2010 Sep 15.

  PMID: 20844233 BACKGROUND

• Pecci A. Pathogenesis and management of inherited thrombocytopenias: rationale for the use of thrombopoietin-receptor agonists. Int J Hematol. 2013 Jul;98(1):34-47. doi: 10.1007/s12185-013-1351-7. Epub 2013 May 1.

  PMID: 23636669 BACKGROUND

• Pecci A, Barozzi S, d'Amico S, Balduini CL. Short-term eltrombopag for surgical preparation of a patient with inherited thrombocytopenia deriving from MYH9 mutation. Thromb Haemost. 2012 Jun;107(6):1188-9. doi: 10.1160/TH12-01-0005. Epub 2012 Mar 8. No abstract available.

  PMID: 22398565 BACKGROUND

• Gerrits AJ, Leven EA, Frelinger AL 3rd, Brigstocke SL, Berny-Lang MA, Mitchell WB, Revel-Vilk S, Tamary H, Carmichael SL, Barnard MR, Michelson AD, Bussel JB. Effects of eltrombopag on platelet count and platelet activation in Wiskott-Aldrich syndrome/X-linked thrombocytopenia. Blood. 2015 Sep 10;126(11):1367-78. doi: 10.1182/blood-2014-09-602573. Epub 2015 Jul 29.

  PMID: 26224646 BACKGROUND

• Favier R, Feriel J, Favier M, Denoyelle F, Martignetti JA. First successful use of eltrombopag before surgery in a child with MYH9-related thrombocytopenia. Pediatrics. 2013 Sep;132(3):e793-5. doi: 10.1542/peds.2012-3807. Epub 2013 Aug 12.

  PMID: 23940247 BACKGROUND

• Fiore M, Saut N, Alessi MC, Viallard JF. Successful use of eltrombopag for surgical preparation in a patient with ANKRD26-related thrombocytopenia. Platelets. 2016 Dec;27(8):828-829. doi: 10.1080/09537104.2016.1190446. Epub 2016 Jun 8. No abstract available.

  PMID: 27276516 BACKGROUND

• Zhang J, Liang Y, Ai Y, Xie J, Li Y, Zheng W. Thrombopoietin-receptor agonists for children with immune thrombocytopenia: a systematic review. Expert Opin Pharmacother. 2017 Oct;18(15):1543-1551. doi: 10.1080/14656566.2017.1373091. Epub 2017 Sep 4.

  PMID: 28845713 BACKGROUND

MeSH Terms

Conditions

Thrombocytopenia; Rare Diseases

Interventions

eltrombopag

Condition Hierarchy (Ancestors)

Blood Platelet Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Cytopenia; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Pierre SIE, Prof.

  University Hospital, Toulouse

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2018
• First Posted: August 20, 2018
• Study Start: August 2, 2019
• Primary Completion: June 27, 2023
• Study Completion: June 27, 2023
• Last Updated: August 27, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (25)