NCT07467252Not yet recruitingPhase 2
AIPH-TB: AI-Optimised Pyrazinamide-Hydroxychloroquine vs Standard RIPE for Drug-Sensitive Pulmonary Tuberculosis - A Phase II RCT
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
Source: ClinicalTrials.gov · Last updated 12 Mar 2026
Brief summary (registry, in English)
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.
- Status (registry)
- Not yet recruiting
- Phase (registry)
- Phase 2
- Study type
- Interventional
- Enrollment
- 200 (estimated)
- First submitted
- 9 Mar 2026
- Start date
- 1 Sept 2026
- Primary completion date
- 31 Dec 2027
- Lead sponsor
- Ministry of Health, Saudi Arabia
- Diseases
- Tuberculosis
- NCT number
- NCT07467252
What you commit to
- Study type: Interventional · Phase 2
- Planned participants: 200
- From 1 Sept 2026 to the primary completion date, 31 Dec 2027
- 1 site in 1 country
- Visits and tests: ask the trial team, the registry does not list them
Built from the registry fields of ClinicalTrials.gov. It describes the study, not your situation.
Who cannot take part
Copied verbatim from ClinicalTrials.gov and grouped by topic. Only the trial team decides who can take part.
Prior treatment
- Concomitant use of medications with significant interactions with study drugs
Other illness
- 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
Lab values
- 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)
Other
- Pregnancy or breastfeeding
- Currently enrolled in another clinical trial
Who the study is looking for
- 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
Age in the registry: 18 years to 65 years · Sex: All · Does not accept healthy volunteers
Sites (1)
Sites in registry order. Pick your city on the disease page to sort them by distance.
| Site | City | Country | Site status |
|---|---|---|---|
| Riyadh First Health Cluster, Ministry of Health Coordinator of this site? Confirm its status | Riyadh | Saudi Arabia | Unknown status |
This page is information, not medical advice. Discuss any trial with your doctor.