Empiric Therapy of Patients With Persistent Fever and Agranulocytosis Using Caspofungin

An Open，Multicenter Clinic Trial of the Effectiveness，Safety and Pharmacokinetics in the Empiric Therapy of Patients With Persistent Fever and Agranulocytosis Using Local Caspofungin

The purpose of this study is evaluating the efficacy and safety of generics caspofungin in the treatment of the patients with neutropenic and fever.Another purpose of this study is comparing the pharmacokinetic characteristics of generics caspofungin and original medicine(Cancidas®) for providing a basis for clinical rational administration.

Study Overview

• Status: Completed
• Conditions: Fungal Infection
• Intervention / Treatment: Drug: Caspofungin

Detailed Description

Caspofungin, a member of the new echinocandin class of compounds，had been proved as effective as and generally better tolerated than liposomal amphotericin B when given as empirical antifungal therapy in patients with persistent fever and neutropenia，and It was approved by FDA in 2001.The generics caspofungin of Chia Tai TianQing Pharmaceutical Group Co. , Ltd. (CTTQ) will be approved by CFDA.The purpose of this study is evaluating the efficacy and safety of this generics caspofungin in the empirical antifungal therapy in patients with persistent fever and neutropenia.

This is a prospective,multicenter,randomized,controlled,open label study,the designed cases are 60 subjects.This study is divided into two stages,one is pharmacokinetics study stage ,the purpose of this stage is comparing the blood concentration of generics caspofungin and original medicine(Cancidas®) ,24 of 60 subjects will participate in this stage,the randomization in a 1:1 ratio will be performed at each group.The other 36 subjects will participate in another stage that is a single study,all subjects will use generics caspofungin.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China
      • Affiliated Concord Hospital of Fujian Medical University
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Jiangsu Province Hospital
    • Suzhou, Jiangsu, China
      • The First Affiliated Hospital of Suzhou University
  • Shandong
    • Jinan, Shandong, China
      • Qilu Hospital of Shandong University
  • Shanghai
    • Shanghai, Shanghai, China
      • Tongji Hospital of Shanghai
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • The First Affiliated Hospital of Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18-70 years old
• The neutrophil counts of the patients with leukemia, lymphoma or other tumors undergoing chemotherapy or receiving hematopoietic stem cell transplantation are below 500 million/L for 96 hours at least,as well as the body temperatures are over 38.0 °C;
• It is ineffective using intravenous broad-spectrum antibacterial therapy lasting at least 96h;
• Estimated survival period > 3 months;
• Subjects voluntarily participate in the study and sign informed consent.

Exclusion Criteria:

• The subjects did not receive adequate antibacterial therapy;
• The subjects were received other antifungal medications within 14 days (except for fluconazole prophylaxis);
• It was confirmed or clinically diagnosed as invasive fungal infection;
• Subjects with liver dysfunction (ALT, AST exceeds the upper limit of normal value by 2 times);
• Subjects with renal insufficiency (Cr, BUN exceeds the upper limit of the normal value of 1.5 times);
• Subjects are allergic to the investigational product;
• Pregnant or lactating women;
• Simultaneous treatment with cyclosporine, tacrolimus, rifampicin, efavirenz, nevirapine, dexamethasone, phenytoin or carbamazepine;
• Other circumstances that investigators believe unsuitable for enrollment; （criteria 8 does not apply to Phase 2）

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm-1; Patients will be assigned to receive intravenous local caspofungin (70 mg on day 1 and 50 mg once daily),If the study therapy was well tolerated but fever persisted for four or more days and the patient's clinical condition deteriorated, the dosage could be increased to 70 mg once daily.For patients who have no evidence of baseline or breakthrough fungal infection, study therapy was administered until the absolute neutrophil count was at least 500 per cubic millimeter and for up to 72 hours thereafter. The onsite investigator determined the duration of therapy for patients with baseline or breakthrough fungal infections; however,it was recommended that treatment be given for at least 14 days and for at least 7 days after neutropenia and symptoms resolved.	Drug: Caspofungin; Considering the possibility of fungal infection, we take empiric therapy for the patients with persistent fever and agranulocytosis using caspofungin for injection.; Other Names: original caspofungin
Active Comparator: Arm-2; Patients will be assigned to receive intravenous original caspofungin (70 mg on day 1 and 50 mg once daily),the therapeutical duration is 4 Days.	Drug: Caspofungin; Considering the possibility of fungal infection, we take empiric therapy for the patients with persistent fever and agranulocytosis using caspofungin for injection.; Other Names: original caspofungin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy evaluation 7 days after drug withdrawal	Curative effect evaluation consists of five parts:The fever subsided during agranulocytosis; Breakthrough invasive fungal infections do not occur during or within 7 days after treatment; If any baseline invasive fungal infection is present, the therapy is effective; The patient was still alive when 7 days after drug withdrawal; The study was not terminated for drug-related toxicity or lacking of efficacy.	7 days after drug withdrawal
Peak Plasma Concentration (Cmax)	The peak plasma concentration after injection of caspofungin	Day1,day3,day4 after the start of the dosing
Half-Life (t 1/2)	The time of duration from the starting of injection to half plasma concentration of caspofungin	Day1 after the start of the dosing
Area under the plasma concentration versus time curve (AUC)	The area under the plasma concentration of caspofungin versus time curve from Day1 to Day4 after the fist dosing	Day1,day3,day4 after the start of the study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The duration of fever	The duration of the fever in patients	7 days after drug withdrawal
Survival rate	The number of surviving patients divided by the total number of patients	7 days after drug withdrawal

Collaborators and Investigators

• Sponsor: Cttq
• Investigators: Principal Investigator: Jianda Hu, Ph.D, Affiliated Concord Hospital of Fujian Medical University

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2018
• Primary Completion (Actual): December 31, 2019
• Study Completion (Actual): December 31, 2019

Study Registration Dates

• First Submitted: November 16, 2018
• First Submitted That Met QC Criteria: February 26, 2019
• First Posted (Actual): February 28, 2019

Study Record Updates

• Last Update Posted (Actual): July 7, 2021
• Last Update Submitted That Met QC Criteria: July 6, 2021
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Hematologic Diseases; Bacterial Infections and Mycoses; Leukopenia; Leukocyte Disorders; Mycoses; Agranulocytosis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antifungal Agents; Caspofungin
• Other Study ID Numbers: CTTQ-CORE-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No