The Combination of Sitagliptin and Danazol as the Treatment of Steroid-resistant/Relapse Immune Thrombocytopenia

The Combination of Sitagliptin and Danazol as the Treatment of Steroid-resistant/Relapse Immune Thrombocytopenia: A Randomized, Controlled, Multicenter, Open-label Trial

Randomized, open-label, multicenter study to compare the efficacy and safety of combination of Sitagliptin and danazol versus danazol for the treatment of adults with steroid-resistant/relapse immune thrombocytopenia (ITP).

Study Overview

• Status: Recruiting
• Conditions: Blood Coagulation Disorders; Thrombocytopenia; Immune Thrombocytopenia; Physiological Effects of Drugs
• Intervention / Treatment: Drug: Danazol; Drug: Sitagliptin

Detailed Description

The investigators are undertaking a parallel group, multicenter, randomized controlled trial of 120 adults with steroid-resistant/relapse ITP in China. Patients were randomized to Sitagliptin plus danazol and danazol monotherapy group. Platelet count, bleeding and other symptoms were evaluated before and after treatment. Adverse events are also recorded throughout the study.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jin Wu, MD; Phone Number: +8617888838056; Email: wujin1996@126.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100010
      • Recruiting
      • Peking University Insititute of Hematology, Peking University People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Primary immune thrombocytopenia (ITP) confirmed by excluding other supervened causes of thrombocytopenia; Platelet count of less than 30×109/L at enrollment; Patients who did not achieve a sustained response to treatment with full-dose corticosteroids for a minimum duration of 4 weeks or who relapsed during steroid-tapering or after its discontinuation; 18 years older;

Exclusion Criteria:

Secondary immune thrombocytopenia (e.g., patients with HIV, HCV, Helicobacter pylori infection or patients with systemic lupus erythematosus) Congestive heart failure Severe arrhythmia Nursing or pregnant women Aspartate aminotransferase and alanine transaminase levels ≥ 3× the upper limit of the normal threshold criteria Creatinine or serum bilirubin levels each 1•5 times or more than the normal range Active or previous malignancy Unable to do blood routine test for the sake of time, distance, economic issues or other reasons.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Danazol; Danazol is given at 200mg bid for 12 weeks.	Drug: Danazol; Oral danazol (200 mg twice daily) for 12 weeks.; Other Names: Danocrine
EXPERIMENTAL: Sitagliptin and Danazol; Sitagliptin is given at a dose of 100 mg/m2 qd for 12 weeks. Danazol is given at 200mg bid for 12 weeks.	Drug: Danazol; Oral danazol (200 mg twice daily) for 12 weeks.; Other Names: Danocrine; Drug: Sitagliptin; Oral Sitagliptin (100mg/m2 daily) for 12 weeks. DPP4 inhibitors have anti-inflammatory, immunomodulatory, and hematopoietic effects in addition to their glycemic regulatory effects. In vivo experiments found that endogenous DPP-4 inhibits megakaryopoiesis, and knockout or inhibition of DPP4 in vivo can enhance the recovery of hematopoietic function after stress. The loss of DPP-4 activity in DPP-4-/-mice mice resulted in an expansion of the megakaryocyte progenitor population in vivo, the recovery time of platelets was shorter than in normal mice after platelet depletion with anti-mouse CD41 antibody. Compared with ordinary mice, the number of platelets increased, which provides a theoretical basis for the use of DPP-4 inhibitors in patients with ITP, and has potential clinical significance.; Other Names: JANUVIA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sustained 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 6-month follow-up. Interim analysis was scheduled at 50% through recruitment.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete remission	The number of participants (responders) with platelet count>=100x10^9/L (CR) and the absence of bleeding.	6 months
Partial remission	The number of participants (responders) with platelet count >=30x10^9/L and at least a 2-fold increase in the baseline count (PR) without the administration of any other platelet increasing therapy.	6 months
Time to response	Time to response was defined as the time from starting treatment to the time to achieve the response.	6 months
Duration of response	Duration of response was measured from the achievement of response to the loss of response.	6 months
Incidence of treatment-emergent adverse events	Adverse events were scaled according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.	6 months

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Investigators: Principal Investigator: Xiao-hui Zhang, MD, Peking University People's Hospital, Peking University Insititute of Hematology

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2021
• Primary Completion (ANTICIPATED): December 1, 2022
• Study Completion (ANTICIPATED): February 1, 2023

Study Registration Dates

• First Submitted: April 25, 2022
• First Submitted That Met QC Criteria: April 25, 2022
• First Posted (ACTUAL): April 29, 2022

Study Record Updates

• Last Update Posted (ACTUAL): April 29, 2022
• Last Update Submitted That Met QC Criteria: April 25, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Sitagliptin; Immune Thrombocytopenia; Danazol
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Hemorrhage; Hemorrhagic Disorders; Skin Manifestations; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura, Thrombocytopenic; Purpura; Hemostatic Disorders; Blood Coagulation Disorders; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Hormone Antagonists; Estrogen Antagonists; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Danazol; Sitagliptin Phosphate
• Other Study ID Numbers: PKU-ITP035

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No