AIPH-TB: AI-Optimised Pyrazinamide-Hydroxychloroquine vs Standard RIPE for Drug-Sensitive Pulmonary Tuberculosis - A Phase II RCT

Starting soon · Phase 2

Conditions studied: Pulmonary Tuberculosis

In brief

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.

Key facts

Study ID

NCT07467252

Run by

Ministry of Health, Saudi Arabia

People needed

200

Starts

2026-09-01

Expected to finish

2028-06-01

Last updated by the study team

2026-03-12

Who can join

Age: 18 and older, up to 65. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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

You may not qualify if…

• 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

Where it is running

• Riyadh First Health Cluster, Ministry of Health — Riyadh, Riyadh Region, Saudi Arabia

Full record on ClinicalTrials.gov

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