Immune thrombocytopenia MedDRA version: 23.0 Level: LLT Classification code 10021245 Term: Idiopathic thrombocytopenic purpura System Organ Class: 100000004851
Conditions
Sponsors
Sykehuset Østfold HF
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: First randomization (Induction phase) 1. Male or female aged =18 years. 2. Diagnosis of primary ITP of less than one-year duration and having a platelet count of = 30 x109/L measured within 4 weeks prior to inclusion with failure to achieve response or relapse after one or more cycles of dexamethasone (40 mg daily for 4 days) or after at least 3 weeks under any other steroid (prednisone or prednisolone). Platelet count between 31 to 50 x109/L is accepted if higher platelet count is required due to concomitant antiplatelet therapy or bleeding. 3. Scheduled intravenous treatment of rituximab. 4. Rituximab infusion will be more than 2 weeks after the first injection of an anti-COVID-19 vaccine. 5. Signed and dated written informed consent. 6. Females of child-bearing potential accepting to follow effective contraceptive methods for at least 12 months following the last administration of rituximab or placebo. Second randomization (maintenance phase) 7. Completion of the induction phase (phase 1) of the study. 8. Sustained response at the end of phase 1. 9. Randomization within: a. 4 weeks after the completion of phase 1, i.e. between week 24 and 28 for a patient who can’t be vaccinated or is already vaccinated against COVID-19 or, b. 16 weeks after the completion of phase 1 if needed to allow the patient to receive anti-COVID-19 vaccine (see Section 10.4.5.2. for vaccination recommendations). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 75 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 55
Exclusion criteria
Exclusion criteria: First randomization (Induction phase) 1. Previous treatment for ITP with: rituximab, other immune suppressants (including mycophenolate mofetil, azathioprin, cyclosporine), dapsone, danazol, thrombopoietin receptor agonist, chemotherapy or splenectomy. 2. Anti-COVID-19 unvaccinated patient with at least one of the following characteristics: a. =65 years old b. Obesity c. Diagnosed Arterial hypertension d. Diagnosed Diabetes mellitus e. Known Kidney disease f. Known Lung disease 3. Pregnancy or lactation. 4. Known active gastro-duodenal ulcer. 5. Secondary ITP: ITP associated with lymphoma, chronic lymphocytic leukemia, drug induced or ITP secondary to autoimmune disorders such as Systemic Lupus Erythematosis, Rheumatoid arthritis or Antiphospholipid syndrome, common variable immune deficiency, human immunodeficiency virus, hepatitis C or thrombocytopenia associated with myeloid dysplasia. 6. Concomitant autoimmune hemolytic anemia. 7. History of any major cardiovascular event within the 6 months prior to randomization, including but not limited to: myocardial infarction, unstable angina, cerebrovascular accident, or New York Heart Association Class III or IV heart failure. 8. Active hepatitis B virus or patients with positive HBsAG or HBcAB. 9. Patients with active severe infection, including systemic mycotic infections or a history of recurring or chronic infections or with underlying conditions which may further predispose patients to serious infection. 10. Known allergy and/or sensitivity or contraindication to rituximab or dexamethasone or any of the ingredients. 11. Patients in a severely immune compromised state. 12. Known contraindication to a treatment with any proton-pump inhibitor. 13. Active malignancy or history of malignant disease during the last 2 years 14. Patients with history of poor compliance or history of alcohol/drug abuse or excessive alcohol beverage consumption that would interfere with the ability to comply with the study protocol, or current or past psychiatric disease that might interfere with the ability to comply with the study protocol or give informed consent. Second randomization (maintenance phase) 1. Severe allergic reaction or serum sickness due to rituximab in phase 1 of the study. 2. Pregnancy. 3. Treatment with rescue medication after week 18. 4. Patients refusing to continue in the study (withdrawal of consent). 5. Splenectomy performed for any cause.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine if maintenance therapy with low-dose rituximab is superior to placebo in prolonging responses among ITP patients who achieved an initial response with rituximab.;Secondary Objective: 1. To explore if the initial overall response rate, at week 24, can be improved by at least 10% by adding dexamethasone to rituximab (induction phase). 2. To assess the safety of study treatment, especially infectious episodes (induction & maintenance phases). 3. To assess bleeding complications during the study (induction & maintenance phases). 4. To assess the use of rescue medications and other platelet-elevating therapies during the study (induction & maintenance phases). 5. To determine rate of sustained Complete Response (CR) (induction & maintenance phases). 6. To determine the duration of overall response and CR (induction & maintenance phases). 7. To assess health-related quality of life and fatigue (induction & maintenance phases).;Primary end point(s): Primary endpoint: sustained overall response during maintenance phase [loss of overall response is defined as: (1) two consecutive measurements with platelet counts < 50 x 109/L taken at 1-8-week interval, and/or, (2) use of any ITP-directed therapies, other than study medication, because of bleeding or thrombocytopenia, except for preoperative elevation of platelet count] (this endpoint applies to maintenance phase only). ;Timepoint(s) of evaluation of this end point: First randomization: 24 weeks and 52 weeks for 2. randomization | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints: 1. Overall response during induction phase defined as mean platelet count, determined in week 24 (± 2 weeks) after induction therapy, > 50 x 109/L, without use of any other ITP-directed therapies after week 18 following the first randomization (this endpoint applies to induction phase only). 2. Safety assessed by the frequency of > grade II adverse events (this endpoint applies to both phases). 3. Grade of bleeding (this endpoint applies to both phases). 4. Sustained Complete Response (CR) during maintenance phase defined as platelet count > 100 x 109/L maintained during maintenance phase, without the use of any ITP-directed therapies 5.Complete Response (CR) during induction phase, defined as platelet count, determined in week 24 (± 2 weeks), > 100 x 109/L without use of any other ITP-directed therapies after week 18 following the first randomization (induction phase) 6.Administration of rescue medication or any other elevating platelet therapy 1. After week 18 (induction phase) 2. During maintenance phase (maintenance phase). 7. Percentage of patients with more than 80% of platelet counts level > 50 x 109/L during the maintenance phase (this endpoint applies to maintenance phase only). 8. Health-related quality of life (this endpoint applies to both phases). 9. Fatigue using an analogical scale of 0-10 and General Fatigue Questionnaire (this endpoint applies to both phases). ;Timepoint(s) of evaluation of this end point: 1.Sustained overall response:24weeks and 52 weeks for 1. and 2.randomization 2.Sustained complete response: 24 weeks and 52 weeks .Rescue medication and remaining endpoints: 18 weeks and 52 weeks | — |
Countries
Denmark, Egypt, France, Norway, Tunisia
Contacts
Public ContactWaleed Ghanima
Sykehuset Østfold HF
Outcome results
None listed