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Study of Adjunctive Recombinant Human Interleukin-2 Therapy in Patients With MDR-TB (rhIL-2)

Primary Purpose

MDR TB

Status
Unknown status
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
RhIL-2
Sponsored by
The First Affiliated Hospital with Nanjing Medical University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for MDR TB focused on measuring MDR-TB, rhIL-2, immunotherapy

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients had/were:

  1. a confirmed case of MDR-TB;
  2. aged 18-70 years old;
  3. a chest CT showing visible lung lesions, with or without holes;
  4. a fasting plasma glucose of less than 7.8 mol/L and a normal fundus examination, if they were diabetic;
  5. voluntarily joined this study and signed an informed consent form.

Exclusion Criteria:

  1. two or more total allergies or any drug or food allergies;
  2. resistant to some drugs of this program;
  3. severe disorders of liver, kidney, or hematologic system functions;
  4. any metabolic diseases, autoimmune diseases, endocrine diseases, cancer, or HIV/AIDS;
  5. a long-term use of immunosuppressive agents;
  6. a blood system dysfunction;
  7. a history of mental illness or epilepsy;
  8. pregnant or lactating;
  9. participated in another clinical trial in the last 3 months or were currently participating in other ongoing clinical trials;
  10. long-term alcohol abuse>10 years and more than two alcoholic drinks per day);
  11. any other factor rendering them unsuitable to participate in this project, such as a history of unreliability.

Sites / Locations

  • the First Affiliated Hospital of Nanjing Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

rhIL-2 Group

Control Group

Arm Description

The patients in rhIL-2 Group were given consisted of four courses of low-dose rhIL-2 plus standard anti-tuberculosis chemotherapy. rhIL-2 (500,000U/m)regiman was given subcutaneously (SC) once every other day (q.o.d.) for 30 days and four courses were carried out separately during months 1, 3, 5, and 7. Standard anti-MDR-TB chemotherapy regiman was totally 24 months,including 6-month Z+KM/AM or CM + PAS/(Pa) + PTO +LFX as an intensive phase treatment, followed by an 18-month Z + LFX + PTO + PAS/(Pa) as a consolidation phase treatment.Then all the group patients were followed up for a minimum of 36 months.

The patients in Control Group were given standard anti-tuberculosis chemotherapy regiman.Standard anti-MDR-TB chemotherapy regiman was totally 24 months,including 6-month Z+KM/AM or CM + PAS/(Pa) + PTO +LFX as an intensive phase treatment, followed by an 18-month Z + LFX + PTO + PAS/(Pa) as a consolidation phase treatment.Then all the group patients were followed up for a minimum of 36 months

Outcomes

Primary Outcome Measures

Cure rate
Completion of treatment and at least five consecutive negative sputum cultures from samples collected at least 30 days apart or one positive sputum culture followed by a minimum of three consecutive negative cultures taken at least 30 days apart during the final 12 months of treatment;

Secondary Outcome Measures

sputum smear/culture conversion rate
The proportions of MDR-TB patients in the two groups achieving sputum smear/culture conversion at the end of 24 months of treatment

Full Information

First Posted
February 19, 2017
Last Updated
February 27, 2017
Sponsor
The First Affiliated Hospital with Nanjing Medical University
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1. Study Identification

Unique Protocol Identification Number
NCT03069534
Brief Title
Study of Adjunctive Recombinant Human Interleukin-2 Therapy in Patients With MDR-TB
Acronym
rhIL-2
Official Title
Study of Adjunctive rhIL-2 Therapy in Patients With MDR-TB That Improves Efficiency and Shortens Course
Study Type
Interventional

2. Study Status

Record Verification Date
September 2009
Overall Recruitment Status
Unknown status
Study Start Date
June 1, 2009 (Actual)
Primary Completion Date
June 1, 2019 (Anticipated)
Study Completion Date
March 1, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The First Affiliated Hospital with Nanjing Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Multidrug-resistant tuberculosis (MDR-TB) has emerged as a challenge worldwide. Few studies have prospectively reported outcomes in patients with pulmonary MDR-TB treated with adjunctive immunotherapy combined to standard chemotherapy. We aimed to assess whether immunotherapy with Interleukin(IL)-2 enhanced the clinical and immune effects of treatment on MDR-TB patients.We performed a multicentre prospective cohort study extend all over Jiangsu province in China. Two groups were generated based on the adjunctive rhIL-2 therapy during 24 months regiman. Bacteriological and imaging data were followed during 24 months with cure rates analysed.
Detailed Description
IL-2 therapy regimans are expected to restore the immune response or to change the immunologic status,thus allowing the host to more efficiently contain and eradicate immune responses, primarily those against cancers and infectious diseases.To address this, we performed a prospective randomized controlled multicenter cohort study of 8-month adjunctive immunotherapy with rhIL-2 for MDR-TB patients compared with the standard chemotherapy. This multicenter prospective clinical study was conducted at 13 tuberculosis centers (coordinating hospital specialized in tuberculosis) across Jiangsu province, China. Joined by the network system of The First Affiliated Hospital of Nanjing Medical University and CDC of Jiangsu province, participants were enrolled from 2009 to 2018. This study protocol was approved by the ethics committee of the First Affiliated Hospital of Nanjing Medical University and was performed adhering to the ethical principles of the Declaration of Helsinki. All patients provided written informed consent before enrollment. The independent data and safety of the study were monitored by the hospital monitoring committee. Patients enrollment Eligible MDR-TB participants were identified by triplicate-spot sputum smears that were positive for acid-fast bacilli and a positive sputum culture with resistance to both isoniazid and rifampin, as determined by susceptibility tests and rapid screening tests . The results of these assays were confirmed using an L-G medium base modified in the Jiangsu province Centers for Disease Control and Prevention(CDC). Treatment plan for the two cohorts: The patients in rhIL-2 group were given consisted of four courses of low-dose rhIL-2 (500,000 U/m) given subcutaneously (SC) once every other day (q.o.d.) for 30 days. Four courses were carried out separately during months 1, 3, 5, and 7. All enrolled patients with pulmonary MDR-TB received a 24-month standard anti-MDR-TB chemotherapy regimen:6-month Z+KM/AM or CM + PAS/(Pa) + PTO +LFX as an intensive phase treatment, followed by an 18-month Z + LFX + PTO + PAS/(Pa) as a consolidation phase treatment. (Z: Pyrazinamide; KM: Kanamycin; AM: Amikacin; CM: Capreomycin; LFX: Levofloxacin; PTO: Prothionamide; PAS: Para-aminosalicylicacid; Pa:Pasiniazid); After finishing treatment regimen patients were followed up for a minimum of 36- months or until discontinuation of regimen, withdrawal of consent, loss to follow-up, death, or end of study. For all of the participants demographic measurements were recorded on the first clinical visit. Patient data were collected at enrollment and quarterly intervals. Sputum smear conversion, sputum culture conversion and chest CT scan improvement were followed up at 3, 6, 12, 18, and 24 months for bacteriological and imaging data collected. Cure rates analysed and compared in both groups. The proportions of MDR-TB patients in the two groups achieving sputum smear/culture conversion, lung lesions absorption were assessed and compared. Safety assessment included clinical symptom observation, Incidences of adverse event (AE )in two groups were assessed and compared. blood routine test, hematologic profile, blood biochemical examination including hepatic aminotransferase and blood ureantrogen/creatinine, blood electrolyte test (potassium, magnesium, calcium), serum thyroid stimulating hormone(TSH), audiology examinations, visual field and color examination. Cure rate was defined as first outcome. Sputum conversion rate was defined as second outcome.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
MDR TB
Keywords
MDR-TB, rhIL-2, immunotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
500 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
rhIL-2 Group
Arm Type
Experimental
Arm Description
The patients in rhIL-2 Group were given consisted of four courses of low-dose rhIL-2 plus standard anti-tuberculosis chemotherapy. rhIL-2 (500,000U/m)regiman was given subcutaneously (SC) once every other day (q.o.d.) for 30 days and four courses were carried out separately during months 1, 3, 5, and 7. Standard anti-MDR-TB chemotherapy regiman was totally 24 months,including 6-month Z+KM/AM or CM + PAS/(Pa) + PTO +LFX as an intensive phase treatment, followed by an 18-month Z + LFX + PTO + PAS/(Pa) as a consolidation phase treatment.Then all the group patients were followed up for a minimum of 36 months.
Arm Title
Control Group
Arm Type
No Intervention
Arm Description
The patients in Control Group were given standard anti-tuberculosis chemotherapy regiman.Standard anti-MDR-TB chemotherapy regiman was totally 24 months,including 6-month Z+KM/AM or CM + PAS/(Pa) + PTO +LFX as an intensive phase treatment, followed by an 18-month Z + LFX + PTO + PAS/(Pa) as a consolidation phase treatment.Then all the group patients were followed up for a minimum of 36 months
Intervention Type
Drug
Intervention Name(s)
RhIL-2
Intervention Description
RhIL-2 treatment intervention was consisted of four courses of low-dose rhIL-2 plus standard anti-tuberculosis chemotharapy. rhIL-2 (500,000 U/m)regimen was given subcutaneously (SC) once every other day (q.o.d.) for 30 days and four courses were carried out separately during months 1, 3, 5, and 7.
Primary Outcome Measure Information:
Title
Cure rate
Description
Completion of treatment and at least five consecutive negative sputum cultures from samples collected at least 30 days apart or one positive sputum culture followed by a minimum of three consecutive negative cultures taken at least 30 days apart during the final 12 months of treatment;
Time Frame
130 months
Secondary Outcome Measure Information:
Title
sputum smear/culture conversion rate
Description
The proportions of MDR-TB patients in the two groups achieving sputum smear/culture conversion at the end of 24 months of treatment
Time Frame
24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients had/were: a confirmed case of MDR-TB; aged 18-70 years old; a chest CT showing visible lung lesions, with or without holes; a fasting plasma glucose of less than 7.8 mol/L and a normal fundus examination, if they were diabetic; voluntarily joined this study and signed an informed consent form. Exclusion Criteria: two or more total allergies or any drug or food allergies; resistant to some drugs of this program; severe disorders of liver, kidney, or hematologic system functions; any metabolic diseases, autoimmune diseases, endocrine diseases, cancer, or HIV/AIDS; a long-term use of immunosuppressive agents; a blood system dysfunction; a history of mental illness or epilepsy; pregnant or lactating; participated in another clinical trial in the last 3 months or were currently participating in other ongoing clinical trials; long-term alcohol abuse>10 years and more than two alcoholic drinks per day); any other factor rendering them unsuitable to participate in this project, such as a history of unreliability.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Qi Tan, PH.D
Phone
+8613584097282
Email
aqua18345760@hotmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hong Wang, PH.D
Organizational Affiliation
the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
Official's Role
Principal Investigator
Facility Information:
Facility Name
the First Affiliated Hospital of Nanjing Medical University
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210029
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Qi Tan, PH.D
Phone
+8613584097282
Email
aqua18345760@hotmail.com
First Name & Middle Initial & Last Name & Degree
Qi Tan, PH.D

12. IPD Sharing Statement

Learn more about this trial

Study of Adjunctive Recombinant Human Interleukin-2 Therapy in Patients With MDR-TB

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