A Multicenter Investigation of Recombinant Human Thrombopoietin (rhTPO) Combining Cyclosporin A Versus Cyclosporin A in Management of Steroid-Resistant/Relapsed Immune Thrombocytopenia （ITP）

Recombinant Human Thrombopoietin (rhTPO) Combining Cyclosporin A Versus Cyclosporin A in Management of Steroid-Resistant/Relapsed Immune Thrombocytopenia （ITP）

The project was undertaking by Qilu Hospital of Shandong University and other 5 well-known hospitals in China. In order to report the efficacy and safety of recombinant human thrombopoietin combining with cyclosporin A for the treatment of adults with refractory immune thrombocytopenia (ITP), compared to cyclosporin A monotherapy.

Study Overview

• Status: Withdrawn
• Conditions: Immune Thrombocytopenia
• Intervention / Treatment: Drug: Cyclosporin A; Drug: rhTPO

Detailed Description

The investigators are undertaking a parallel group, multicenter, randomized controlled trial of 120 steroid-resistant/relapsed ITP adult patients from 6 medical centers in China. One part of the participants are randomly selected to receive recombinant human thrombopoietin (given subcutaneously at a dose of 300 Units/kg for 14 consecutive days, following with a flexible dosage depending on platelet count until the 29th day), combining with cyclosporin A (given orally at a dose of 1.5-2.0mg/kg twice daily for 3 consecutive months, adjusted to maintain serum levels between 200-400 ng/ml and tapered by 50 mg/d per week if patients achieved a complete response). The others are selected to receive cyclosporin A monotherapy (given orally at a dose of 1.5-2.0mg/kg twice daily for 3 consecutive months, adjusted to maintain serum levels between 200-400 ng/ml and tapered by 50 mg/d per week if patients achieved a complete response). Platelet count, bleeding and other symptoms were evaluated before and after treatment. Adverse events are also recorded throughout the study. In order to report the efficacy and safety of the combination therapy compared to cyclosporin A monotherapy for the treatment of adults with steroid-resistant/relapsed ITP.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250012
      • Qilu Hospital, Shandong University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Meet the diagnostic criteria for immune thrombocytopenia.
2. Steroid-resistant/relapsed hospitalized patients, may be male or female, between the ages of 18-80 years.
3. To show a platelet count < 30×10^9/L, and with bleeding manifestations.
4. Eastern Cooperative Oncology Group（ECOG）performance status ≤ 2.
5. Willing and able to sign written informed consent

Exclusion Criteria:

1. Received chemotherapy or anticoagulants or other drugs affecting the platelet counts within 3 months before the screening visit.
2. Current HIV infection or hepatitis B virus or hepatitis C virus infections. 3.Severe medical condition (lung, hepatic or renal disorder) other than ITP. 4.Unstable or uncontrolled disease or condition related to or impacting cardiac function (e.g., unstable angina, congestive heart failure, uncontrolled hypertension or cardiac arrhythmia)

5.Female patients who are nursing or pregnant, who may be pregnant, or who contemplate pregnancy during the study period.

6.Have a known diagnosis of other autoimmune diseases, established in the medical history and laboratory findings with positive results for the determination of antinuclear antibodies, anti-cardiolipin antibodies, lupus anticoagulant or direct Coombs test.

7.Patients who are deemed unsuitable for the study by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: combination treatment group; 60 enrolled patients are randomly picked up to take cyclosporin A in combination with rhTPO at the indicated dose.	Drug: Cyclosporin A; given orally at a dose of 1.5-2.0mg/kg twice daily for 3 consecutive months, adjusted to maintain serum levels between 200-400 ng/ml and tapered by 50 mg/d per week if patients achieved a complete response.; Drug: rhTPO; given subcutaneously at a dose of 300 Units/kg for 14 consecutive days, following with a flexible dosage depending on platelet count until the 29th day
Active Comparator: single treatment group; 60 enrolled patients are randomly picked up to take cyclosporin A at the indicated dose.	Drug: Cyclosporin A; given orally at a dose of 1.5-2.0mg/kg twice daily for 3 consecutive months, adjusted to maintain serum levels between 200-400 ng/ml and tapered by 50 mg/d per week if patients achieved a complete response.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of platelet response (No Response)	NR.No response (NR) was defined as platelet count < 30 × 10^9/L or a less than two fold increase in platelet count from baseline or the presence of bleeding. Platelet count must be measured on two occasions more than a day apart.	The time frame is up to 3 months per subject
Evaluation of platelet response (Complete Response)	CR. A complete response (CR) was defined as a sustained (≥ 3 months) platelet count ≥ 100×10^9/L	The time frame is up to 3 months per subject
Evaluation of platelet response (Response)	R. A response (R) was defined as a sustained (≥ 3 months) platelet count ≥ 30×10^9/L without recurrence of thrombocytopenia.	The time frame is up to 3 months per subject
Evaluation of platelet response (relapses)	A relapses was defined as platelet count falls below 30×10^9/L or bleeding accrues after achieving R or CR.	The time frame is up to 3 months per subject

Secondary Outcome Measures

Outcome Measure	Time Frame
The number and frequency of therapy associated adverse events The number and frequency of therapy associated adverse events The number and frequency of therapy associated adverse events The number and frequency of therapy associated adverse events	up to 3 months per subject

Collaborators and Investigators

• Sponsor: Shandong University

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Anticipated): July 1, 2015

Study Registration Dates

• First Submitted: July 27, 2014
• First Submitted That Met QC Criteria: July 27, 2014
• First Posted (Estimate): July 29, 2014

Study Record Updates

• Last Update Posted (Estimate): April 20, 2016
• Last Update Submitted That Met QC Criteria: April 18, 2016
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: Immune Thrombocytopenia; Cyclosporin A; Recombinant Human Thrombopoietin
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Hemorrhage; Hemorrhagic Disorders; Blood Coagulation Disorders; Skin Manifestations; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura, Thrombocytopenic; Purpura; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Antifungal Agents; Calcineurin Inhibitors; Cyclosporine; Cyclosporins
• Other Study ID Numbers: ITP-Cyclosporin A