AC-PTLD Trial

Recruitment & Eligibility

Status: Pending

Sex: All

Target Recruitment: 484

Inclusion Criteria

1. Persons aged 18 to 65 years
2. Willing and able to provide signed written consent or witnessed oral consent with thumbprint
in the case of illiteracy, prior to undertaking any trial-related procedures.
3. Body weight (in light clothing without shoes) between 30 and 90 kg.
4. Xpert TB/RIF OR Ultra showing RIF-S-MTB, with subsequent confirmation of MTB by culture.
5. Chest radiograph meeting criteria for moderate or far advanced pulmonary tuberculosis 1
6. FEV1 =65% of predicted based on age, height, sex, and race
7. If female, of child-bearing potential and sexually active, willing to use an effective contraceptive
method for the duration of study participation
8. HIV-1/2 seronegative, OR if seropositive, CD4 T cell count =100/µl AND willing to either continue
or start ART during study participation
9. Negative SARS-CoV-2 Ag, or if positive, with D-dimer <1.0 mg/

Exclusion Criteria

1. Any condition for which participation in the trial, as judged by the investigator, could compromise
the well-being of the subject or prevent, limit or confound protocol specified assessments,
such as pneumothorax or clinically significant pleural effusion.
2. Current or imminent (within 24 hr) treatment for malaria.
3. Pregnancy or breastfeeding
4. Is critically ill, and in the judgment of the investigator has a diagnosis likely to result in death
during the trial or the follow-up period.
5. TB meningitis or other forms of severe tuberculosis with high risk of a poor outcome as judged
by the investigator.
6. History of allergy or hypersensitivity to any of the trial therapies or related substances, including
known allergy or suspected hypersensitivity to rifampin.
7. Having participated in other clinical trials with investigational agents within 8 weeks prior to
trial start or currently enrolled in an investigational trial.
8. No more than 5 days treatment for the current TB episode, and no other TB treatment in the
preceding 6 months
9. Angina pectoris requiring treatment with nitroglycerin or other nitrates
10. Cardiac arrhythmia requiring medication, or any clinically significant ECG abnormality, in the
opinion of the investigator
11. Random blood glucose >140 mg/dL (7.8mmol/L), or history of unstable Diabetes Mellitus
which required hospitalization for hyper- or hypoglycaemia within the past year prior to start
of screening.
12. Use of systemic corticosteroids within the past 28 days, or likely to require systemic corticosteroids
for another medical condition during the study period.
13. Patients requiring treatment with medications not compatible with rifampin, such as HIV protease
inhibitors
14. Subjects with any of the following abnormal laboratory values:a. creatinine >2 mg/dL (176.84umol/L)
b. haemoglobin <8 g/dL
c. platelets <100x109 cells/L
d. serum potassium <3.5 mmol/l
e. aspartate aminotransferase (AST) =2.0 x ULN
f. alkaline phosphatase (AP) >5.0 x ULN
g. total bilirubin >1.5 mg/dL (25.65umol/L)
h. positive HbsAg

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
1. FEV1% of predicted at month 12

Secondary Outcome Measures

Name	Time	Method
2. FEV1%, FVC%, and FEV/FVC at other time points and as summary measures over time using mixed effects modeling;<br>3. Number/severity of respiratory exacerbations<br>4. Respiratory symptoms/quality of life (QoL)<br>5. Whole blood oxidized/reduced glutathione at multiple time points<br>6. Mtb sputum culture status at 2, 3, 6 months after enrolment<br>7. Change in MGIT TTP over time<br>8. Treatment failure/TB recurrence<br>9. Number/severity of hepatic safety events 10. Number/severity of SAEs/SUSARS 11. Sputum and blood biomarkers -Exploratory outcome