A Study of Switching Avatrombopag and Rh-TPO in ITP

Study Overview
=================
Brief Summary
-----------------
Thrombopoietin receptor agonists (TPO-RAs) represent a highly effective and well-tolerated second-line ITP treatment that provides excellent responses.If there is cross-resistance between 2 drugs for the treatment of adult ITP is still unkonwn.The purpose of this study is to investigate the efficacy and safety of switching avatrombopag and rh-TPO in adults with ITP.

Detailed Description
-----------------
Thrombopoietin Receptor Agonists (TPO-RAs) are novel treatments for patients with chronic Primary Immune Thrombocytopenia (ITP). According to the findings of mechanism-based studies, rhTPO competes with endogenous TPO for binding to TPO-R while avatrombopag has an additive effect with endogenous TPO, indicating that the treatment mechanism and side-effect profiles could be somewhat different between these drugs. If there is cross-resistance between 2 drugs for the treatment of adult ITP is still no answer. The purpose of this study is to investigate the efficacy and safety of switching avatrombopag and rh-TPO in adults with ITP.This is a non-interventional study. Patients who fail previous steroids and receive rh-TPO and then switch to avatrombopag or vice versa will be enrolled. The reason for switch will be recorded. The efficacy, safety, and patient/physician preference will be assessed and compared between the two agents.

Official Title
-----------------
A Prospective Observational Study of Switching Avatrombopag and Rh-TPO in Chinese Adult Patients With Primary Immune Thrombocytopenia

Conditions
-----------------
Corticosteroid-resistant or Relapsed ITP

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1.18 years or older 2.Primary ITP 3.Failed initial glucocorticosteroid treatment, 4.Applying rhTPO or Eltrombopag as subsequent treatment 5.Switch from rh-TPO to eltrombopag or vice versa 6.Normal neutrophils 7.Available follow-up at least 6 weeks after switching Exclusion Criteria: HIV positive status, or active infection of HBV or HCV Suffering from a serious or progressive disease, which, in the investigator's judgment, put the subject at undue risk for participation in this study (i.e. cancer or pre-cancer, immunocompromised, uncontrolled diabetes, epilepsy, severe cardio-cerebrovascular disease(s) (i.e. stroke, idiopathic aortic stenosis, aneurysm, hypertrophic obstructive cardiomyopathy, ischaemic heart disease, tachyarrhythmias, severe heart failure [classified as NYHA III-IV], severe lung dysfunctions, etc)) History of thrombosis plus two or more risk factors as defined in Caprini thrombosis risk assessment model Lactating or pregnant women, or WOCBP who are unwilling to use highly effective contraceptive measures during the study period Abnormal liver and renal functions: AST or ALT or total bilirubin ≥1.5 × ULN, and/or creatinine ≥176.8 μmol/L Women of childbearing potential (WOCBP) that are pregnant or wish to become pregnant during the prospective phase of the study. Other conditions which the investigator considers inappropriate for enrollment

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Recombinant human thrombopoietin (rh-TPO) group<br>Patients who fail previous steroids and avatrombopag and then switch to Rh-TPO will be enrolled. The reason for switch will be recorded. Patients will be given rh-TPO 300 U/kg once daily for 14 days as initial treatment. After initial treatment, maintenance therapy were performance. At initial therapy, rhTPO will be suspended when platelet counts ≥100×10^9 / L. During maintenance therapy, patients with platelet counts >150×10^9 / L will suspend treatment until platelet counts drop to ≤150×10^9 / L. Dosing interval will be prolonged when platelet count is ≥100×10^9 / L to ≤150×10^9 / L. Dose modification is not required when platelet count is ≥30×10^9 / L to <100×10^9 / L. The efficacy, safety, and patient/physician preference will be assessed. | |
| Avatrombopag group<br>Patients who fail previous steroids and rh-TPO and then switch to avatrombopag will be enrolled. The reason for switch will be recorded. Patients will be given avatrombopag 20mg once daily as initiate treatment, and adjust the dosage according to the count of platelets. The maximum dose of avatrombopag is 40mg daily.Avatrombopag will be terminated any time the platelet counts increased above 250×10^9/L. Dose adjustment of avatrombopag will be allowed to maintain platelet counts between 30×10^9/L and 150×10^9/L. The efficacy, safety, and patient/physician preference will be assessed. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Initial response after switching | Rate of response at 4 weeks after switching from rhTPO to avatrombopag or vise versa | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate at 12 weeks after switching | Rate of response at 12 weeks after switching from rhTPO to avatrombopag or vise versa | 12 weeks | 
| Initial response after switching according to the reasons of switching | Rate of response at 1 month after switching according to the reasons of switching,such as lack of efficacy, Platelet count fluctuations, development of adverse events,patient's or doctor's preference | 4 weeks | 
| Rate of response at 12 weeks after switching according to the reasons of switching | Rate of response at 12 weeks after switching according to the reasons of switching,such as lack of efficacy, Platelet count fluctuations, development of adverse events,patient's or doctor's preference | 12 weeks | 
| Time to response | Time to CR or R from switching | 4 weeks | 
| Durable response | The maintenance of platelet count ≥ 30 x 10^9/L, at least 2-fold increase of the baseline count, the absence of bleeding, and no need for rescue medication at the 24 weeks follow-up. | 24 weeks | 
| Incidence of bleeding events | Incidence of clinically significant bleeding as assessed using the world health organization (WHO) bleeding scale | 24 weeks | 
| Immune Thrombocytopenia Patient Assessment Questionnaire (ITP-PAQ) | In all participants ,use ITP-PAQ to assess the Health Related Quality of Life(HRQoL) before and after treatment. | 24 weeks | 
| Functional Assessment of Chronic Illness Therapy fatigue subscale (FACIT-F) | In all participants ,use FACIT-F to assess the Health Related Quality of Life(HRQoL) before and after treatment. | 24 weeks | 
| Safety assessment | Number of Participants with side effects of the drugs | 24 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Immune Thrombocytopenia, Recombinant human thrombopoietin, avatrombopag, switching