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Antibiotic

Short-course TB Drug Regimens for Tuberculosis (CRUSH-TB Trial)

Phase 2 & 3

Recruiting

Research Sponsored by Centers for Disease Control and Prevention

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

For participants with HIV: current use of dolutegravir-based ART (Anti Retroviral Therapy), or ability and willingness to start or transition to a dolutegravir-based antiretroviral therapy regimen

Documentation of negative HIV status within the past 3 months prior to enrollment or documentation confirming HIV infection

Must not have

Known or suspected resistance to isoniazid or rifamycins

Known family history of Long QT Syndrome in a first-degree relative

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 8 weeks and 12 weeks

Awards & highlights

No Placebo-Only Group

Summary

This trial tests whether 2 x 17-week regimens of TB drugs are as effective as the standard 6-month regimen. 288 male/female participants will be followed up to 78 weeks post-randomization.

Who is the study for?

This trial is for individuals with pulmonary tuberculosis, including those with HIV if their CD4 count is above 100 cells/mm3. Participants must be at least 12 years old, have a negative pregnancy test if applicable, and agree to use reliable contraception. Exclusion criteria include certain heart conditions, inability to take oral meds, recent TB treatment or drug resistance.

What is being tested?

The study tests two short-course treatments against standard six-month therapy for TB. One group receives bedaquiline, moxifloxacin, pyrazinamide plus rifabutin (BMZRB) for four months; another gets the same drugs plus delamanid (BMZD). The control group follows the conventional regimen of isoniazid and rifampin (2HRZE/4HR).

What are the potential side effects?

Potential side effects may include liver issues due to Rifabutin and Delamanid; nerve damage from Isoniazid; digestive problems from Pyrazinamide; tendon damage from Moxifloxacin; blood disorders from Bedaquiline. Ethambutol can cause vision issues while Rifampin may lead to flu-like symptoms.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am on or willing to start dolutegravir-based HIV treatment.

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I have recent proof of my HIV status, whether negative or positive.

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My CD4 T cell count is at least 100 cells/mm3.

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I am 12 years old or older.

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I am a woman who is not surgically sterilized or post-menopausal and have a recent negative pregnancy test.

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I have tuberculosis in my lungs, possibly affecting other areas except my brain or bones.

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I need some help but can take care of most of my personal needs.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My condition is resistant to certain TB medications.

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A close family member has Long QT Syndrome.

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I have a serious liver condition.

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I have or might have bone tuberculosis.

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I have had an aortic aneurysm or dissection.

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I cannot take medications by mouth.

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I have been treated for tuberculosis for more than 5 days in the last 6 months.

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I am not taking any medications that would interfere with the study drugs.

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I have or might have tuberculosis in my brain or spinal cord.

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I haven't taken TB medication for more than 5 days in the last month.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 8 weeks and 12 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~8 weeks and 12 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and 8 weeks and 12 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Time to sputum culture negative in liquid media after study treatment among participants in Experimental Regimens (2 BZMRb/ 2 BMRb, Arm 1) and (2 BMZD/ 2 BMD, Arm 2) compared to Control (2HRZE/4HR, Arm 3) in modified intention-to-treat group (ITT)

Secondary study objectives

All-cause study drug discontinuation among participants in experimental regimens compared to control regimen

Clearance of bedaquiline

Proportion of participants with sputum culture negative by 8 weeks and by 12 weeks (solid and liquid media) in all 3 regimens

+6 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Active Control

Group I: 2BMZRb/2 BMRbExperimental Treatment4 Interventions

Eight weeks of daily treatment with bedaquiline (B or BDQ), moxifloxacin (M), pyrazinamide (Z), plus rifabutin (Rb), followed by nine weeks of daily treatment with bedaquiline (B or BDQ), moxifloxacin (M) and Rifabutin (Rb) All drugs are administered orally, seven days/week, directly observed by a health care worker at least five of the seven days each week. Pyridoxine (vitamin B6), 25 or 50 mg, is administered once daily. Study drug doses: Bedaquiline (B): 200 mg once daily x 56 days, then 100 mg daily; Moxifloxacin (M): 400 mg once daily; Pyrazinamide (Z) 1500 mg (weight \<75kg) or 2000mg(\> 75kg) once daily x 56 days; Rifabutin (Rb): 300 mg once daily

Group II: 2 BMZD/2 BMDExperimental Treatment4 Interventions

Eight weeks of daily treatment with bedaquiline (B or BDQ), moxifloxacin (M), pyrazinamide (Z), plus delamanid (D or DLM) followed by nine weeks of daily treatment with bedaquiline (B or BDQ), moxifloxacin (M) and delamanid (D or DLM) All drugs are administered orally, seven days/week, directly observed by a health care worker at least five of the seven days each week. Pyridoxine (vitamin B6), 25 or 50 mg, is administered once daily. Study drug doses: Bedaquiline (B): 200 mg once daily x 56 days, then 100 mg daily; Moxifloxacin (M): 400 mg once daily; Pyrazinamide (Z) 1500 mg (weight \<75kg) or 2000mg(\> 75kg) once daily x 56 days; Delamanid (D):300 mg once daily

Group III: 2RHZE/4RHActive Control4 Interventions

Eight weeks of daily treatment with rifampin, isoniazid, pyrazinamide, and ethambutol, followed by eighteen weeks of daily treatment with rifampin and isoniazid All drugs are administered orally, seven days/week, directly observed by a health care worker at least five of the seven days each week. Pyridoxine (vitamin B6), 25 or 50 mg, is administered once daily study drug doses: Rifampin (R), 600 mg daily; Isoniazid (H), 300 mg daily; Pyrazinamide (Z) 1500 mg (weight \<75kg) or 2000mg(\> 75kg) once daily ; Ethambutol, 15 mg/kg once daily rounded up to nearest 400 mg dose

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Delamanid

2016

Completed Phase 3

~1570

Bedaquiline

2020

Completed Phase 3

~4020