Tests a new pyrazinamide and hydroxychloroquine plan against standard TB treatment
Compares a new drug combination with standard treatment in adults with lung tuberculosis.
Plain-language title generated from the registry record
Registry title: AIPH-TB: AI-Optimised Pyrazinamide-Hydroxychloroquine vs Standard RIPE for Drug-Sensitive Pulmonary Tuberculosis - A Phase II RCT
Key facts
- Where
- Riyadh, Saudi ArabiaSee the site
- Phase
- Phase 2
Could this be for you?
Answer for yourself. This is not a decision: only the study team can say whether you can take part.
- Are you between 18 and 65 years old?
Source: NCT07467252, who can take part
Where in Saudi Arabia
- Riyadh First Health Cluster, Ministry of HealthRiyadh, Saudi ArabiaNo longer taking part
Questions to ask the study team
- How often do I need to come in, and for how long each time?
- Are travel costs paid?
- Can I keep my own doctor?
- What happens if I want to stop?
Trial details
- Who runs it
- Ministry of Health, Saudi Arabia
- Trial code
- NCT07467252
- Record updated
- 12 March 2026
- Original description
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.Read full original descriptionShow less
A Phase II, Open-Label, Randomised, Parallel-Group, Active-Controlled Trial Evaluating the Efficacy, Safety, and Tolerability of AI-Optimised Pyrazinamide 1,500 mg / Hydroxychloroquine 200 mg Twice Daily (AIPH-TB Protocol) Versus Standard Four-Drug RIPE Regimen in Adults With Newly Diagnosed Drug-Sensitive Pulmonary Tuberculosis
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.
Inclusion: 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: Concomitant use of medications with significant interactions with study drugs; Drug-resistant tuberculosis (confirmed resistance to Rifampicin or Isoniazid); Known hypersensitivity to Pyrazinamide, Hydroxychloroquine, or any RIPE drugs; Retinal disease or known contraindications to Hydroxychloroquine; Extrapulmonary tuberculosis as the primary site; 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); Pregnancy or breastfeeding; Currently enrolled in another clinical trial.