AIPH-TB: AI-Optimised Pyrazinamide-Hydroxychloroquine vs Standard RIPE for Drug-Sensitive Pulmona… (NCT07467252) | Clinical Trial Compass
Not Yet RecruitingPhase 2
AIPH-TB: AI-Optimised Pyrazinamide-Hydroxychloroquine vs Standard RIPE for Drug-Sensitive Pulmonary Tuberculosis - A Phase II RCT
Saudi Arabia200 participantsStarted 2026-09
Plain-language summary
Tuberculosis (TB) kills 1.3 million people annually and remains the world's deadliest bacterial disease. The standard four-drug RIPE regimen achieves only 85% cure rates and causes drug-induced hepatotoxicity in 25-37% of patients. Hydroxychloroquine (HCQ), an FDA-approved antimalarial, has been shown to synergise with pyrazinamide (PZA) by inhibiting the BCRP-1 efflux pump and raising phagolysosomal pH, increasing intracellular PZA concentrations (FICI 0.38 in vitro). The AIPH-TB computational framework (Artificial Intelligence Physicochemical Harmonisation for Tuberculosis) uses multi-objective reinforcement learning, Gaussian process regression, and a digital twin macrophage simulator to identify an AI-optimised dosing schedule that maximises this synergy (PZA 1,500 mg + HCQ 200 mg at 0800 and HCQ 200 mg at 2000), maintaining phagolysosomal pH within 5.2-5.8 for 18 of 24 hours. The computational model predicts FICI 0.28 (strongly synergistic), 9.4-fold increase in intracellular PZA concentration, 99.5% cure rate, and \<1.5% hepatotoxicity. This Phase II randomised controlled trial will test whether the AI-optimised PYZ-HCQ protocol is superior to standard RIPE in 200 newly-diagnosed drug-sensitive pulmonary TB patients over 6 months of treatment with 6 months of follow-up.
Who can participate
Age range
18 Years – 65 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion Criteria:
* Confirmed diagnosis of drug-sensitive pulmonary tuberculosis (bacteriologically confirmed by positive sputum smear microscopy or GeneXpert MTB/RIF)
* Age 18 to 65 years
* Naive to anti-tuberculosis treatment (no previous TB treatment or less than 1 month of TB treatment in the past)
* Willing to provide written informed consent
* Able to comply with study visits and procedures
* HIV-negative or HIV-positive with CD4 count ≥200 cells/mm³ on stable antiretroviral therapy
Exclusion Criteria:
* Drug-resistant tuberculosis (confirmed resistance to Rifampicin or Isoniazid)
* Severe hepatic impairment (Child-Pugh Class C) or ALT/AST \>3 times upper limit of normal
* Severe renal impairment (eGFR \<30 mL/min/1.73m²)
* Known hypersensitivity to Pyrazinamide, Hydroxychloroquine, or any RIPE drugs
* Pregnancy or breastfeeding
* Retinal disease or known contraindications to Hydroxychloroquine
* Concomitant use of medications with significant interactions with study drugs
* Extrapulmonary tuberculosis as the primary site
* Currently enrolled in another clinical trial
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.