NCT05972772 Rickettsia Clearance Study
| NCT ID | NCT05972772 |
| Status | Recruiting |
| Phase | Phase 2, Phase 3 |
| Sponsor | Lao-Oxford-Mahosot Hospital Wellcome Trust Research Unit |
| Condition | Infectious Disease |
| Study Type | INTERVENTIONAL |
| Enrollment | 72 participants |
| Start Date | 2024-11-01 |
| Primary Completion | 2025-08-31 |
Eligibility & Interventions
Eligibility Fast-Check
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What to Expect as a Participant
You will actively receive the study intervention — which may be a drug, biologic, device, or procedure.
In Phase 2, researchers evaluate early signs of effectiveness. You may be randomized to receive the active treatment or a comparator. Monitoring continues closely.
This trial targets 72 participants in total. It began in 2024-11-01 with a primary completion date of 2025-08-31.
⚠ This information is for research awareness only. Always consult your physician before joining any clinical trial. Participation is voluntary and you may withdraw at any time.
Brief Summary
Murine typhus is a disease caused by Rickettisa typhi, an obligate intracellular bacterium transmitted by rodent fleas. The disease has a worldwide distribution; however the true burden is unknown, related to its non-specific presentation and lack of access to diagnosis in many regions. A systematic review of untreated murine typhus based on observational studies of a total of 239 patients has estimated the mortality associated with the disease at between 0.4% and 3.6%. Scrub typhus is caused by Orientia tsutsugamushi and transmitted by the larval stage of chigger mites (Trombiculidae family). It has been estimated to affect at least one million people each year. A systematic review found varying reports of the mortality associated with untreated scrub typhus ranging from 0-70% (median 6%). Polymerase chain reaction (PCR) based diagnosis of rickettsial infections is only available in one centre (Mahosot Hospital) in Vientiane. A number of hospitals use a variety of point-of-care antibody tests to diagnose rickettsial infections however many of these have not been validated and they are of uncertain sensitivity and specificity. In 2006 results of a two year prospective study of 427 patients presenting to Mahosot Hospital with a febrile illness and negative blood cultures showed that 115 (27%) patients had an acute rickettsial infection, confirmed by serological testing. Among these patients, 41 were diagnosed with murine typhus and 63 with scrub typhus. Antibacterial agents with activity against rickettsial pathogens include doxycycline, azithromycin, chloramphenicol and rifampicin. Azithromycin is often reserved for pregnant women or children below the age of 8 years due to lasting concerns after the tetracycline-associated staining of growing bones and teeth in the past. Evidence is accumulating that doxycycline is superior to azithromycin for the treatment of rickettsial disease. Clinical treatment failures have occurred following azithromycin treatment of murine typhus. The relationship between rickettsial bacteria load and both disease severity and response to treatment has not been characterised. Rickettsial concentrations in blood are generally low, of the order of 210 DNA copies/mL blood for R. typhi and 284 DNA copies/mL blood for O. tsutsugamushi. At present, there is no standard antibiotic susceptibility testing (AST) method for R. typhi and O. tsutsugamushi. The gold standard method for AST for Rickettsia pathogens is the plaque assay which determines minimal inhibitory concentration (MICs) from the smallest antimicrobial concentration inhibiting rickettsial plaque forming unit formation. This method is laborious and time consuming, taking approximately 14-16 days based on species to yield a result. Molecular detection methods are useful for diagnosing patients infected with rickettsial pathogens and has been applied for antibiotic susceptibility testing. Antibiotic susceptibility testing based on DNA synthesis inhibition detecting by quantitative PCR (qPCR) for O. tsutsugamushi clinical isolates has been reported. However, the relationship between antibiotic susceptibility profiles and treatment response has not been studied. There is a need to develop a reliable ex vivo method to characterize the treatment response and compare susceptibility of R. typhi and O. tsutsugamushi to different agents.
Eligibility Criteria
Inclusion Criteria: * Age above or equal 18 years * Able to take oral medication * Rapid test positive for murine typhus or scrub typhus * Agrees to stay in hospital for at least 36 hours and to attend for scheduled follow up visits * Written informed consent to participate in the study * A negative urinary pregnancy test for all women of child-bearing age Exclusion Criteria: * Pregnancy or breast feeding * Previous allergic reaction to doxycycline or azithromycin * Received more than one dose of chloramphenicol, doxycycline, tetracycline, fluoroquinolones, rifampicin or azithromycin during this hospital admission or more than one dose of any of these drugs in the week before admission * Contraindication to doxycycline: severe hepatic impairment, known SLE * Contraindication to azithromycin: sever hepatic impairment * Severe typhus defined as the presence of one or more of the following: 1. Reduced level of consciousness 2. Clinical jaundice 3. Shock (BP systolic \<80 mmHg) 4. Unable to take oral medication 5. Radiological evidence of pneumonia 6. Clinical evidence for meningitis/encephalitis or the need of LP 7. Alternative diagnosis confirmed that explains the presenting symptoms 8. Any other syndrome which in the opinion of the admitting doctor constitutes severe typhus (reason must be stated)
Contact & Investigator
Weerawat Phuklia, PhD
PRINCIPAL INVESTIGATOR
Lao-Oxford-Mahosot Hospital Wellcome Trust Research Unit
Frequently Asked Questions
Who can join the NCT05972772 clinical trial?
This trial is open to participants of all sexes, aged 18 Years or older, studying Infectious Disease. Full inclusion and exclusion criteria are listed in the Eligibility Criteria section. Always confirm your eligibility with the research team before applying.
What phase is the NCT05972772 trial and what does that mean for participants?
Phase 2 trials evaluate whether the treatment shows signs of effectiveness while continuing to monitor safety. More participants are enrolled than in Phase 1 to help refine the treatment protocol.
Is NCT05972772 currently recruiting?
Yes, NCT05972772 is actively recruiting participants. Contact the research team at weerawat@tropmedres.ac for enrollment information.
Where is the NCT05972772 trial being conducted?
This trial is being conducted at Vientiane, Laos, Vientiane Province, Laos.
Who is sponsoring the NCT05972772 clinical trial?
NCT05972772 is sponsored by Lao-Oxford-Mahosot Hospital Wellcome Trust Research Unit. The principal investigator is Weerawat Phuklia, PhD at Lao-Oxford-Mahosot Hospital Wellcome Trust Research Unit. The trial plans to enroll 72 participants.