A New Treatment for Primary Smear-positive Pulmonary Tuberculosis With Interleukin-2

A Randomized Multicenter Clinical Trial of a New Treatment for Primary Smear- Positive Pulmonary Tuberculosis With Interleukin-2

The purpose of the study is to compare the efficacy and safety of standard chemotherapy regimen 2HRZE/4HR plus IL-2 and standard regimen 2HRZE/4HR for newly diagnosed smear positive pulmonary tuberculosis.

Study Overview

• Status: Recruiting
• Conditions: Tuberculosis, Pulmonary
• Intervention / Treatment: Drug: Interleukin-2

Detailed Description

1. Design:The study is a multi-center, randomized, controlled, open clinical trial.
2. Population:Initial smear positive pulmonary tuberculosis patients who fulfill the inclusion and exclusion criteria.

3. Investigational regimens:

   Experimental group regimen:2HRZE/4HR+Interleukin-2 （500000 units daily, subcutaneous injection in the first month） The control group regimen: 2HRZE/4HR Dosage: isoniazid 300mg(given once daily),rifampin 450mg(less than 50kg,given once daily) or 600mg(more than 50kg,given once daily),pyrazinamide 1500mg(less than 50kg,given once daily) or 30mg/kg(more than 50kg,given once daily),ethambutol 750mg(less than 50kg,given once daily) or 1000mg(more than 50kg,given once daily).

4. Primary and Secondary outcome measures:

primary efficacy outcome measures:(a)Negative conversion rate of sputum bacteria. (b)Sputum smear conversion proportion at the treatment completion .

secondary efficacy outcome measure:Recurrence rate after treatment.

• Study Type: Interventional
• Enrollment (Anticipated): 1100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Naihui Chu, PhD; Email: dongchu1994@sina.com

Study Locations

• China
  • Anhui
    • Fuyang, Anhui, China, 230000
      • Recruiting
      • the Second hospital of Fuyang
      • Contact: haiqing Liu; Phone Number: 13855894607
  • Fujian
    • Fuzhou, Fujian, China, 350000
      • Recruiting
      • Fuzhou Chest Hospital
      • Contact: xiaohong Chen; Phone Number: 13275013012
  • Guangzhou
    • Shenzhen, Guangzhou, China, 518000
      • Recruiting
      • Shenzhen Third People's Hospital
      • Contact: qunyi Deng; Phone Number: 13823145706
  • Guizhou
    • Guiyang, Guizhou, China, 550000
      • Recruiting
      • Guiyang Public Health Treatment Center
      • Contact: jing Chen; Phone Number: 13985410691
  • Hebei
    • Handan, Hebei, China, 056000
      • Recruiting
      • The Infectious Hospital of Handan
      • Contact: chunyan Zhang; Phone Number: 15803200615
    • Shijiazhuang, Hebei, China, 050000
      • Recruiting
      • Hebei Chest Hospital
      • Contact: zhihui Li; Phone Number: 13833465658; Email: lzhihui2011@126.com
  • Heilongjiang
    • Jiamusi, Heilongjiang, China, 154000
      • Recruiting
      • Jiamusi Insititute For Tuberculosis Control
      • Contact: chao Qiu; Phone Number: 13039651567
    • Mudanjiang, Heilongjiang, China, 150000
      • Recruiting
      • The Infectious Hospital of mudanjiang
      • Contact: lixiang Chu; Phone Number: 18645753107
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Recruiting
      • Zhengzhou Sixth People's Hospital
      • Contact: yu Chen; Phone Number: 13823145706
  • Hunan
    • Changsha, Hunan, China, 410000
      • Recruiting
      • the central hospital of Changsha
      • Contact: chunxiang Li; Phone Number: 13055161267
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • Recruiting
      • The people's hospital of Jiangsu province
      • Contact: Hong Wang
  • Jiangxi
    • Nanchang, Jiangxi, China, 330000
      • Recruiting
      • Jiangxi Chest Hospital
      • Contact: aihua Deng; Phone Number: 13307096301
  • Liaoning
    • Dalian, Liaoning, China, 110000
      • Recruiting
      • Dalian Tuberculosis Hospital
      • Contact: Qing Ji; Phone Number: 13009482267
  • Shandong
    • Qingdao, Shandong, China, 266000
      • Recruiting
      • Qingdao Chest Hospital
      • Contact: yufeng Liu
      • Contact: Phone Number: 13863985511
  • Shanxi
    • Taiyuan, Shanxi, China, 030000
      • Recruiting
      • Taiyuan Fourth People's Hospital
      • Contact: quanhong Wang; Phone Number: 13934242762
    • Xi'an, Shanxi, China, 710000
      • Recruiting
      • Xian Chest Hospital
      • Contact: liyun Dang; Phone Number: 18091888085

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Is willing and able to give informed consent to participate in the trial treatment and follow-up (signed or witnessed consent if the patient is illiterate).
2. Is aged 18-65 years.
3. Chest X-ray showed that there were active tuberculosis foci in the lungs with one of the following cases: (1) sputum specimens (or sputum and bronchial lavage fluid) were 2+ once or 1+ twice ; (2) sputum smear positive and sputum X-pert positive.
4. Newly diagnosed cases receiving anti-TB treatment for less than one month.
5. No other immune preparations （such as: thymosin，IFN-y，BCG-PSN，Mycobacterium vaccae，Utilins，lentinan ）were used in the past 3 months.
6. the urine analysis of Women of childbearing age are negative and agree to use the efficient contraception during the study period.

Exclusion Criteria:

1. Has a known allergy to any drug of treatment regimens.
2. There are serious complications or impaired renal function (serum creatinine is 1.5 times higher than the normal limit) or impaired liver function (ALT or AST levels are 3 times higher than the normal limit); hemoglobin is less than 7.0g/dl. Platelets less than 50x109/L.
3. Complication with Diabetic.
4. The screening diagnosis was isoniazid resistance or rifampin resistance
5. There are serious cardiovascular diseases, such as heart failure, hypertension, arrhythmia or post myocardial infarction state.
6. Is known to be pregnant or breast-feeding.
7. Karnofsky score is less than 50%.
8. Is taking any clinical trial in the past 3 months.
9. Is critically ill, and in the judgment of the investigator, not fit for the study or unlikely to complete the full course of study.
10. HIV is positive or AIDS patients.
11. Has Non tuberculous mycobacterial lung disease.
12. Merge with extra pulmonary tuberculosis.

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: experimental group; Experimental group regimen:2H(Isoniazid)R(Rifampicin)Z(Pyrazinamide)E(Ethambutol)/4HR+Interleukin-2 （500000 units daily, subcutaneous injection in the first month） Dosage: isoniazid 300mg(given once daily),rifampin 450mg(less than 50kg,given once daily) or 600mg(more than 50kg,given once daily),pyrazinamide 1500mg(less than 50kg,given once daily) or 30mg/kg(more than 50kg,given once daily),ethambutol 750mg(less than 50kg,given once daily) or 1000mg(more than 50kg,given once daily).	Drug: Interleukin-2; Interleukin 2 (IL-2) is a pleiotropic cytokine that is produced after antigen activation and plays crucial roles in the immune response. IL-2 secreted by activated T cells is central to the development of an immune response to infection, promoting the differentiation and proliferation of lymphoid cells. This hydrophobic molecule and the various cytokines that it elicits regulates the behavior of T and B lymphocytes, monocytes/macrophages, natural killer (NK) cells, and neutrophils. IL-2 therapy regimens are expected to limit mycobacterial replication. Early clinical trials with IL-2 demonstrated that IL-2 immunotherapy may be useful in controlling infectious disease.; Other Names: IL-2
Active Comparator: Control regimen group; The control group regimen: 2H(Isoniazid)R(Rifampicin)Z(Pyrazinamide)E(Ethambutol)/4HR Dosage: isoniazid 300mg(given once daily),rifampin 450mg(less than 50kg,given once daily) or 600mg(more than 50kg,given once daily),pyrazinamide 1500mg(less than 50kg,given once daily) or 30mg/kg(more than 50kg,given once daily),ethambutol 750mg(less than 50kg,given once daily) or 1000mg(more than 50kg,given once daily).	Drug: Interleukin-2; Interleukin 2 (IL-2) is a pleiotropic cytokine that is produced after antigen activation and plays crucial roles in the immune response. IL-2 secreted by activated T cells is central to the development of an immune response to infection, promoting the differentiation and proliferation of lymphoid cells. This hydrophobic molecule and the various cytokines that it elicits regulates the behavior of T and B lymphocytes, monocytes/macrophages, natural killer (NK) cells, and neutrophils. IL-2 therapy regimens are expected to limit mycobacterial replication. Early clinical trials with IL-2 demonstrated that IL-2 immunotherapy may be useful in controlling infectious disease.; Other Names: IL-2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary study endpoint was the proportion of subjects who had converted their sputum cultures to negative at the end of treatment.	A cure was defined as who was smear- or culture-negative in the last month of treatment and on at least one previous occasion. Treatment completion was defined as patients who completed treatment but who does not have a negative sputum smear or culture result in the last month of treatment and on at least one previous occasion. Treatment failure was defined as patients whose sputum smear or culture is positive at 5 months or later during treatment.	two-month course intensive phase treatment, followed by a four-month consolidation phase treatment.Some TB patients with cavity should receive 9 total months (7 months of continuation therapy after the initial 2-month intensive phase).

Collaborators and Investigators

• Sponsor: Beijing Chest Hospital
• Investigators: Principal Investigator: Naihui Chu, PhD, Beijing Chest Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2016
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: December 20, 2017
• First Submitted That Met QC Criteria: February 20, 2021
• First Posted (Actual): February 23, 2021

Study Record Updates

• Last Update Posted (Actual): February 23, 2021
• Last Update Submitted That Met QC Criteria: February 20, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: pulmonary tuberculosis; clinical trial; interleukin-2
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Tuberculosis, Pulmonary; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antineoplastic Agents; Interleukin-2
• Other Study ID Numbers: 2015ZX10003001-002