ACTIVE_NOT_RECRUITING

Short-course Regimens for the Treatment of Pulmonary Tuberculosis

Conditions

Tuberculosis, Pulmonary Tuberculosis Infection

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The purpose of this study is to determine whether one or two 17-week regimens of tuberculosis treatment bedaquiline (B or BDQ), moxifloxacin (M), pyrazinamide (Z)-- (BMZ) plus either Rifabutin (Rb) or Delamanid (D or DLM) are as effective as a standard six-month regimen for treatment of pulmonary tuberculosis (TB). All three regimens are administered daily, seven days each week. The first 17-week regimen is 2 months of bedaquiline (B or BDQ), moxifloxacin (M), pyrazinamide (Z), (BMZ) plus rifabutin (Rb) (BMZRB) followed by 2 months of bedaquiline (B or BDQ), moxifloxacin (M) and Rifabutin (Rb) (2 BMZRb/2 BMRb, Arm 1) The Second 17-week regimen is 2 months of bedaquiline (B or BDQ), moxifloxacin (M), pyrazinamide (Z), (BMZ) plus delamanid (D or DLM); (BMZD) followed by 2 months of bedaquiline (B or BDQ), moxifloxacin (M) and delamanid (D or DLM) (2 BMZD/2 BMD, Arm 2) The standard 26-week treatment control regimen which is two months of isoniazid, rifampin, ethambutol, and pyrazinamide (2HRZE) followed by four months of isoniazid and rifampin (4HR); (2HRZE/4HR, Arm 3) Target enrollment is 288 male and female participants (96/arm). participants. Participants will be followed until 78 weeks post-randomization, or until the last enrolled participant completes 52 weeks post-randomization, whichever comes first.

Official Title

Phase 2C Clinical Trial of Novel, Short-course Regimens for the Treatment of Pulmonary Tuberculosis: CRUSH-TB (Combination Regimens for Shortening TB Treatment)

Quick Facts

Study Start:2023-11-21

Study Completion:2027-12-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT05766267

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:12 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Pulmonary tuberculosis with or without suspected or proven concomitant extrapulmonary tuberculosis outside the central nervous system or bones 2. Acid-fast bacilli (AFB) seen in an expectorated sputum specimen at least 1+ or positive GeneXpert (or GeneXpert Ultra) for M. tuberculosis, with semiquantitative results of "medium" or "high". 3. Age ≥12 years 4. Documentation of negative HIV status within the past 3 months prior to enrollment or documentation confirming HIV infection. 5. For participants with HIV: 1. current use of dolutegravir-based ART (Anti Retroviral Therapy), or ability and willingness to start or transition to a dolutegravir-based antiretroviral therapy regimen 2. CD4 T cell count greater than or equal to 100 cells/mm3 based on testing performed at or within 30 days prior to study enrollment 6. Written informed consent/assent 7. Karnofsky score of at least 60 ("requiring some help, can take care of most personal requirements") 8. A verifiable address or residence location that is readily accessible for visiting, and willingness to inform the study team of any change of address during the treatment and follow-up period. 9. For all women who have not undergone a surgical sterilization procedure or who do not meet the study definition of post-menopausal, a negative pregnancy test at or within seven (7) days prior to screening 10. For all individuals of child-bearing potential who are not surgically sterilized, agreement to practice a reliable method of contraception (barrier method or non-hormonal intrauterine device) or abstain from sexual activity that could lead to pregnancy while receiving study drug treatment and for 30 days after stopping study treatment	1. Pregnant or breast-feeding 2. More than 5 days of tuberculosis treatment in the previous 6 months 3. Previous treatment with any drug or combination of drugs known to have activity against M. tuberculosis (e.g., isoniazid, rifamycins, pyrazinamide, ethambutol, fluoroquinolones, etc.) for more than five days in the thirty days prior to enrollment 4. Unable to take oral medications 5. Hypersensitivity or previous intolerance to any of the study drugs 6. Current or planned use of medications that have unacceptable drug-drug interactions with any of the study drugs during study treatment 7. Suspected or proven central nervous system tuberculosis 8. Suspected or proven bone tuberculosis 9. Screening ECG with QTcF \>450 for men or \>470 for women (Note: in case of hypokalemia or hypomagnesemia, ECG can be repeated following electrolyte supplementation) 10. Clinically significant ECG abnormality in the opinion of the site investigator, including but not limited to second or third degree atrioventricular (AV) block, prolongation of the QRS complex over 120 ms (in both male and female participants), or clinically important arrhythmia 11. Current clinically relevant cardiovascular disorder in the opinion of the site investigator, including but not limited to heart failure, coronary heart disease, arrhythmia, or tachyarrhythmia 12. Known family history of Long QT Syndrome in a first-degree relative (i.e., parent, offspring, or sibling) 13. History of aortic aneurysm or dissection 14. Hepatic cirrhosis or other serious liver disease 15. Other medical conditions, that, in the investigator's judgment, make study participation not in the individual's best interest. 16. Laboratory parameters done at or within 14 days prior to screening: 1. Serum or plasma alanine aminotransferase greater than 3 times the upper limit of normal 2. Serum or plasma total bilirubin greater than 2.5 times the upper limit of normal 3. Serum creatinine \> 2 times the upper limit of normal 4. Platelet count \< 75,000 cells/mm3 5. Absolute neutrophil count \<1,000 cells/mm3 6. Serum or plasma potassium \<3.5 meq/L (note: potassium may be repleted and test repeated) 17. Weight less than 40.0 kg 18. Known or suspected resistance to isoniazid or rifamycins (by phenotypic or molecular test) 19. Previously enrolled in this study or currently enrolled in another therapeutic clinical trial that, in the investigator's judgment, would compromise study integrity or participant safety 20. Current or planned incarceration or other involuntary detention.

Inclusion Criteria

Exclusion Criteria

1. Pulmonary tuberculosis with or without suspected or proven concomitant extrapulmonary tuberculosis outside the central nervous system or bones
2. Acid-fast bacilli (AFB) seen in an expectorated sputum specimen at least 1+ or positive GeneXpert (or GeneXpert Ultra) for M. tuberculosis, with semiquantitative results of "medium" or "high".
3. Age ≥12 years
4. Documentation of negative HIV status within the past 3 months prior to enrollment or documentation confirming HIV infection.
5. For participants with HIV:
1. current use of dolutegravir-based ART (Anti Retroviral Therapy), or ability and willingness to start or transition to a dolutegravir-based antiretroviral therapy regimen
2. CD4 T cell count greater than or equal to 100 cells/mm3 based on testing performed at or within 30 days prior to study enrollment
6. Written informed consent/assent
7. Karnofsky score of at least 60 ("requiring some help, can take care of most personal requirements")
8. A verifiable address or residence location that is readily accessible for visiting, and willingness to inform the study team of any change of address during the treatment and follow-up period.
9. For all women who have not undergone a surgical sterilization procedure or who do not meet the study definition of post-menopausal, a negative pregnancy test at or within seven (7) days prior to screening
10. For all individuals of child-bearing potential who are not surgically sterilized, agreement to practice a reliable method of contraception (barrier method or non-hormonal intrauterine device) or abstain from sexual activity that could lead to pregnancy while receiving study drug treatment and for 30 days after stopping study treatment

1. Pregnant or breast-feeding
2. More than 5 days of tuberculosis treatment in the previous 6 months
3. Previous treatment with any drug or combination of drugs known to have activity against M. tuberculosis (e.g., isoniazid, rifamycins, pyrazinamide, ethambutol, fluoroquinolones, etc.) for more than five days in the thirty days prior to enrollment
4. Unable to take oral medications
5. Hypersensitivity or previous intolerance to any of the study drugs
6. Current or planned use of medications that have unacceptable drug-drug interactions with any of the study drugs during study treatment
7. Suspected or proven central nervous system tuberculosis
8. Suspected or proven bone tuberculosis
9. Screening ECG with QTcF \>450 for men or \>470 for women (Note: in case of hypokalemia or hypomagnesemia, ECG can be repeated following electrolyte supplementation)
10. Clinically significant ECG abnormality in the opinion of the site investigator, including but not limited to second or third degree atrioventricular (AV) block, prolongation of the QRS complex over 120 ms (in both male and female participants), or clinically important arrhythmia
11. Current clinically relevant cardiovascular disorder in the opinion of the site investigator, including but not limited to heart failure, coronary heart disease, arrhythmia, or tachyarrhythmia
12. Known family history of Long QT Syndrome in a first-degree relative (i.e., parent, offspring, or sibling)
13. History of aortic aneurysm or dissection
14. Hepatic cirrhosis or other serious liver disease
15. Other medical conditions, that, in the investigator's judgment, make study participation not in the individual's best interest.
16. Laboratory parameters done at or within 14 days prior to screening:
1. Serum or plasma alanine aminotransferase greater than 3 times the upper limit of normal
2. Serum or plasma total bilirubin greater than 2.5 times the upper limit of normal
3. Serum creatinine \> 2 times the upper limit of normal
4. Platelet count \< 75,000 cells/mm3
5. Absolute neutrophil count \<1,000 cells/mm3
6. Serum or plasma potassium \<3.5 meq/L (note: potassium may be repleted and test repeated)
17. Weight less than 40.0 kg
18. Known or suspected resistance to isoniazid or rifamycins (by phenotypic or molecular test)
19. Previously enrolled in this study or currently enrolled in another therapeutic clinical trial that, in the investigator's judgment, would compromise study integrity or participant safety
20. Current or planned incarceration or other involuntary detention.

Contacts and Locations

Principal Investigator

Kelly Dooley, MD

STUDY_CHAIR

Johns Hopkins University

Daniel W Fitzgerald, MD

STUDY_CHAIR

Weill Medical College of Cornell University

Ekaterina V Kurbatova, MD, PhD, MPH

STUDY_CHAIR

Centers for Disease Control and Prevention

Wendy Carr, PhD

STUDY_CHAIR

Centers for Disease Control and Prevention

Study Locations (Sites)

TBTC Site 26 Seattle & King County TB Control Program

Seattle, Washington, 98104

United States

Collaborators and Investigators

Sponsor: Centers for Disease Control and Prevention

Kelly Dooley, MD, STUDY_CHAIR, Johns Hopkins University
Daniel W Fitzgerald, MD, STUDY_CHAIR, Weill Medical College of Cornell University
Ekaterina V Kurbatova, MD, PhD, MPH, STUDY_CHAIR, Centers for Disease Control and Prevention
Wendy Carr, PhD, STUDY_CHAIR, Centers for Disease Control and Prevention

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-11-21

Study Completion Date2027-12-31

Study Record Updates

Study Start Date2023-11-21

Study Completion Date2027-12-31

Terms related to this study

Additional Relevant MeSH Terms

Tuberculosis, Pulmonary
Tuberculosis Infection