Enhanced Treatment Strategy for Disseminated MAC Infection in HIV Patients: A Randomized Controlled Trial

NCT07585461 | Not Yet Recruiting

• 1 other identifier: DMAC-RCT-2026
• Study Type: interventional
• Target: 124
• Locations: 0 countries
• Sites: N/A

Brief Summary

Background: Disseminated Mycobacterium avium complex (MAC) infection remains a serious opportunistic infection in patients with advanced HIV infection, particularly among those with severe immunosuppression. Despite the widespread use of antiretroviral therapy (ART), disseminated MAC (DMAC) continues to be associated with significant morbidity and mortality. The current standard treatment consists of a macrolide-based triple regimen, including a macrolide, ethambutol, and rifamycin. However, in patients with high mycobacterial burden or profound immunodeficiency, early microbiological response and clinical improvement are often suboptimal, and treatment is complicated by drug interactions and tolerability issues. Objective: This study aims to evaluate whether adding a fluoroquinolone (levofloxacin or moxifloxacin) to the standard triple therapy improves early clinical outcomes in HIV-infected patients with disseminated MAC infection. Methods: This is a prospective, multicenter, randomized, open-label, controlled trial. A total of 124 adult HIV-infected patients with confirmed disseminated MAC infection will be randomly assigned in a 1:1 ratio to receive either standard triple therapy (macrolide, ethambutol, and rifamycin) or an intensified four-drug regimen with the addition of a fluoroquinolone during the initial 8-week intensive phase. Participants will be followed for at least 24 weeks. Outcomes: The primary endpoint is the clinical symptom resolution rate at Day 28. Secondary endpoints include microbiological outcomes (culture or molecular conversion at Days 28, 56, and 84), time to culture conversion, mortality, relapse, and safety outcomes including adverse events and QT interval prolongation. Significance: This study will provide prospective evidence on whether an intensified treatment strategy can improve early clinical response and microbiological clearance in disseminated MAC infection, while maintaining an acceptable safety profile. The findings may help optimize treatment strategies for HIV-associated disseminated MAC infection.

Conditions

Disseminated Mycobacterium Avium Complex Infection; Opportunistic Infections, HIV Related

Keywords

Disseminated MAC; HIV; Fluoroquinolone

Outcome Measures

Primary Outcomes (1)

• Clinical Symptom Resolution Rate at Day 28

  The proportion of participants achieving clinical symptom resolution at Day 28. Clinical symptom resolution is defined as meeting all of the following criteria: 1. absence of fever for at least 48 hours without the use of antipyretics; 2. improvement in systemic symptoms, defined as a ≥50% reduction in total symptom score or all individual symptom scores ≤1; 3. stabilization or increase in body weight compared with baseline; 4. no requirement for escalation or modification of antimycobacterial therapy due to disease progression; 5. survival through Day 28. Participants who do not meet all criteria, require rescue therapy, or die before Day 28 are classified as non-responders.

  Day 28 (±3 days)

Study Arms (2)

Standard Triple Therapy

ACTIVE COMPARATOR

Participants receive standard triple therapy for disseminated Mycobacterium avium complex infection, consisting of a macrolide (azithromycin or clarithromycin), ethambutol, and rifabutin. Antiretroviral therapy is continued or initiated according to standard clinical practice and drug-drug interaction assessment.

Drug: Standard Triple Therapy

Standard Triple Therapy Plus Fluoroquinolone

EXPERIMENTAL

Participants receive standard triple therapy for disseminated Mycobacterium avium complex infection, consisting of a macrolide (azithromycin or clarithromycin), ethambutol, and rifabutin, plus a fluoroquinolone (levofloxacin or moxifloxacin) during the initial 8-week intensive phase. The fluoroquinolone is selected at baseline based on clinical considerations and is intended to remain unchanged during the intensive phase unless modification is required for safety reasons. Antiretroviral therapy is continued or initiated according to standard clinical practice and drug-drug interaction assessment.

Drug: Experimental: Standard Triple Therapy Plus Fluoroquinolone

Interventions

Standard Triple Therapy DRUG

Standard triple therapy for disseminated MAC infection consisting of a macrolide, ethambutol, and rifabutin, administered according to protocol-defined dosing and duration.

Also known as: Azithromycin, Clarithromycin, Ethambutol, Rifabutin

Standard Triple Therapy

Experimental: Standard Triple Therapy Plus Fluoroquinolone DRUG

Participants receive standard therapy for disseminated Mycobacterium avium complex infection plus a fluoroquinolone during the initial 8-week intensive phase.

Also known as: Azithromycin, Ethambutol, Rifabutin, Levofloxacin, Moxifloxacin, clarithromycin

Standard Triple Therapy Plus Fluoroquinolone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years
• HIV infection confirmed
• Disseminated Mycobacterium avium complex (MAC) infection confirmed by positive culture from a sterile site or positive molecular/sequencing-based detection from a sterile site specimen considered clinically significant
• Systemic manifestations consistent with disseminated infection
• Planned initiation of standard antimycobacterial therapy
• Able and willing to provide written informed consent

You may not qualify if:

• Prior effective antimycobacterial treatment for \>14 days before enrollment
• Known macrolide resistance, if susceptibility data are available
• Hypersensitivity to macrolides, ethambutol, rifamycins, or fluoroquinolones
• Baseline QTc \>500 ms or history of significant cardiac arrhythmia
• Uncorrected hypokalemia or hypomagnesemia
• History of severe adverse reaction to fluoroquinolones, such as tendon rupture or severe neuropathy
• Severe hepatic impairment or severe renal dysfunction precluding study treatment
• Concomitant medications that significantly prolong QT interval and cannot be safely discontinued
• Pregnancy or breastfeeding
• Coexisting infection requiring non-protocol antimycobacterial therapy, such as active tuberculosis
• Any condition that, in the investigator's judgment, would interfere with study participation or interpretation of results

Sponsors & Collaborators

• Shanghai Public Health Clinical Center: lead

MeSH Terms

Conditions

AIDS-Related Opportunistic Infections

Interventions

Azithromycin; Clarithromycin; Ethambutol; Rifabutin; Fluoroquinolones; Levofloxacin; Moxifloxacin

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Opportunistic Infections; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Ethylenediamines; Diamines; Polyamines; Amines; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Ofloxacin

Central Study Contacts

Li LIU, M.D.

CONTACT

8618916091026; liuli@shaphc.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D

Study Record Dates

• First Submitted: April 14, 2026
• First Posted: May 13, 2026
• Study Start: April 30, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: May 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Beginning 6 months and ending 5 years following article publication.