A Phase 4 interventional study of Acyclovir (ACV) and Placebo in Autoimmune Rheumatic Diseases, Recurrent Herpes Simplex and Prevention, sponsored by University of Sao Paulo General Hospital. Recruiting at 1 site in Brazil. Open to participants aged 12 Years and older. Per ClinicalTrials.gov, last updated 2026-08-05.
Sponsored by University of Sao Paulo General Hospital · Phase 4, Interventional, and Prevention
The goal of this randomized, double-blind, placebo-controlled clinical trial is to evaluate the effectiveness and safety of oral suppressive therapy with acyclovir in preventing herpes simplex virus (HSV) reactivation in patients with autoimmune rheumatic diseases (ARDs) who have a history of recurrent HS episodes.
The main questions this study aims to answer are:
Does continuous oral acyclovir reduce the frequency of HSV reactivation in ARD patients compared to placebo? What is the safety profile of prolonged acyclovir use in this population? What are the main risk factors (clinical and treatment-related) associated with HSV reactivation in immunosuppressed patients.
Participants will:
Be randomly assigned (1:1) to receive oral acyclovir (400 mg BID) or placebo for 12 months; Be followed for a total of 24 months, with regular clinical evaluations (every 3 months) and laboratory monitoring (every 3 months); Be assessed for HSV recurrence based on clinical symptoms, detection of HSV DNA by polymerase chain reaction (PCR) in mucocutaneous swabs in doubtful cases, and standardized reporting forms; Undergo disease activity assessments and adverse event monitoring at regular intervals.
The study includes adult and pediatric patients with confirmed diagnoses of one of the following ARDs: systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), dermatomyositis/polymyositis (DM/PM), systemic sclerosis (SSc), systemic vasculitis, primary Sjögren's syndrome, Mixed connective tissue disease (MCTD), Chronic recurrent multifocal osteomyelitis (CRMO), Sarcoidosis and Behçet's Syndrome. All participants must have a documented history of recurrent HSV (oral and/or genital) before inclusion.
HSV-1 and HSV-2 are ubiquitous human pathogens that can establish lifelong latency, with the potential for frequent reactivation. Immunocompromised individuals, including patients with ARDs, are particularly vulnerable to more severe and disseminated HSV infections, which may result in significant morbidity and even mortality. Despite this, the true incidence and burden of HSV reactivation in ARD patients under immunosuppression remain underexplored.
Previous studies in solid-organ transplant recipients and people living with HIV have demonstrated that prophylactic or suppressive antiviral therapy with acyclovir can significantly reduce HSV-related complications. However, no randomized controlled trials to date have evaluated the efficacy and safety of this approach in ARD patients under frequent immunosuppressive drug use and recurrent HSV in this group.
This trial will enroll 62 participants with ARDs and prior recurrent HSV infection, randomly assigned to receive oral acyclovir or placebo for 12 months, followed by continued monitoring for an additional year. Primary outcomes include the number of clinically confirmed HSV reactivations in acyclovir and placebo groups. Secondary outcomes include safety (adverse events), treatment tolerability, and identification of clinical and therapeutic risk factors for HSV recurrence.
By providing high-quality evidence through a rigorously controlled methodology, this study seeks to fill a critical knowledge gap in rheumatology, offering practical guidance for antiviral prophylaxis in immunosuppressed ARD patients, ultimately improving patient safety and clinical outcomes in a vulnerable population.
166 studies on the registry are indexed under Herpes Simplex; 12 are open to participants now.
This study's planned enrollment of 62 is close to the median of 66 across 113 interventional studies indexed under Herpes Simplex.
Browse Herpes Simplex studies →University of Sao Paulo General Hospital is the lead sponsor of 611 studies on the registry; 98 are open to participants now.
Of its 8 completed or terminated interventional studies of FDA-regulated products, 0 (0%) have results posted.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria
-Participants will be excluded if they have a known to acyclovir or any component of the study medication.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients with autoimmune rheumatic diseases and a history of recurrent HS will receive oral acyclovir 400 mg twice a day for 12 months. ARD patients will be randomly assigned in a 1:1 ratio, with the use of an automated Web and telephone system, to one of two subgroups: ACV or Placebo.
Drug: Acyclovir (ACV)
Patients with autoimmune rheumatic diseases and a history of recurrent HS will receive oral placebo twice a day for 12 months. ARD patients will be randomly assigned in a 1:1 ratio, with the use of an automated Web and telephone system, to one of two subgroups: ACV or Placebo.
Other: Placebo
Oral acyclovir 400 mg twice a day for 12 months. Acyclovir is a synthetic nucleoside analog with in vitro activity against HSV-1, HSV-2, VZV, and other herpesviruses.
Matching oral placebo, administered twice a day for 12 months.
HSV Reactivation Rate
Proportion of patients with autoimmune rheumatic diseases (ARDs) and history of recurrent HS who experience clinical reactivation of HSV (oral and/or genital) during the 12-month treatment period and during the following 12 months. Reactivation will be defined by clinical signs and symptoms of HS, detection of HSV DNA by PCR in mucocutaneous swabs in doubtful cases.
Time frame: Baseline to Month 24
Safety Profile - Adverse Events (AEs)
Frequency and severity of adverse events (e.g., gastrointestinal discomfort, headache, rash) reported during the 12-month treatment phase.
Time frame: Day 1 through Month 12
Frequency of Serious Adverse Events (SAEs)
Incidence of SAEs (hospitalization, death, drug-related complications) in the acyclovir and placebo groups.
Time frame: Day 1 through Month 12
Treatment Discontinuation Due to AEs
Proportion of participants who discontinue acyclovir or placebo due to adverse events.
Time frame: Day 1 through Month 12
Time to First HSV Reactivation
Number of days from randomization to first documented HSV reactivation.
Time frame: Day 1 through Month 12
Factors Associated with HSV Reactivation
Analysis of clinical (disease activity) and treatment-related factors (e.g., corticosteroid dose, immunosuppressive drugs and biologic therapy) associated with increased risk of HSV reactivation.
Time frame: Day 1 through Month 24
Disease Activity Flares - Systemic Lupus Erythematosus
Systemic Lupus Erythematosus (SLE): An increase of more than three points in the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). Score: 0 - No activity; 1 - 4 mild activity; \> 6 high activity
Time frame: Day 1 through Month 12
Disease Activity Flares - Rheumatoid Arthritis
Rheumatoid Arthritis (RA): An absolute increase in Disease Activity Score - C-reactive protein (DAS28-CRP) \> 1.2, or an increase in DAS28-CRP \> 0.6 if baseline DAS28-CRP \> 3.2.
Time frame: Day 1 through Month 12
Disease Activity Flares - Juvenile Idiopathic Arthritis
Juvenile Idiopathic Arthritis (JIA): An increase in Juvenile Arthritis Disease Activity Score (JADAS-27) \> 5 points, or clinical worsening of ≥ 2 active joints requiring therapy escalation, in accordance with ACR Pediatric Response criteria.
Time frame: Day 1 through Month 12
Disease Activity Flares - Ankylosing Spondylitis
Ankylosing Spondylitis (AS): An increase in Ankylosing Spondylitis Disease Activity Score (ASDAS) \> 0.9.
Time frame: Day 1 through Month 12
Disease Activity Flares - Psoriatic Arthritis
Psoriatic Arthritis (PsA): Worsening in disease activity classification by Disease Activity Index for Psoriatic Arthritis (DAPSA). If the patient was already in the worst status, clinical judgment and therapy increments were applied. For the following diseases, the definition of flare relied on clinical judgment and the need for increased therapy, supported by various disease scores.
Time frame: Day 1 through Month 12
Disease Activity Flares - Dermatomyositis/Polymyositis
Dermatomyositis/Polymyositis (DM/PM): Based on the International Myositis Assessment and Clinical Studies Group (IMACS) core set: Myositis Disease Activity Assessment (MYOACT), Health Assessment Questionnaire (HAQ), Patient's and Physician's Visual Analog Scales (VAS), ACR/EULAR Myositis Response Criteria (MRC) and the MMT8.
Time frame: Day 1 through Month 12
Disease Activity Flares - Systemic Sclerosis
Systemic Sclerosis (SSc): Increase in the modified Rodnan skin score, development of new digital ulcers, worsening dyspnea classified by NYHA functional scale, or increase in the EULAR Systemic Sclerosis Impact of Disease Index (ScleroID).
Time frame: Day 1 through Month 12
Disease Activity Flares - Systemic Vasculitis
Systemic Vasculitis (ANCA-associated vasculitis, including granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, and microscopic polyangiitis): Increase in Birmingham Vasculitis Activity Score (BVAS).
Time frame: Day 1 through Month 12
Disease Activity Flares - Primary Sjögren's Syndrome
Primary Sjögren's Syndrome (SjD): EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI).
Time frame: Day 1 through Month 12
Disease Activity Flares - Mixed Connective Tissue Disease
Mixed Connective Tissue Disease (MCTD): Increase in the Kahn \& Appelboam MCTD Activity Score.
Time frame: Day 1 through Month 12
Disease Activity Flares - Chronic Recurrent Multifocal Osteomyelitis
Chronic Recurrent Multifocal Osteomyelitis (CRMO): Recurrence or emergence of ≥ 1 new bone lesion confirmed by MRI, or increase ≥ 2 points in the Pediatric/Adult CRMO Activity Score (PCAS/ACAS), accompanied by the need for escalation of anti-inflammatory or disease-modifying therapy.
Time frame: Day 1 through Month 12
Disease Activity Flares - Sarcoidosis
Sarcoidosis: Increase ≥ 2 points in the Sarcoidosis Activity Assessment Tool (SAAT) or worsening in the Sarcoidosis Clinical Activity Classification (SCAC), defined by recurrence or progression of pulmonary infiltrates, increase in serum ACE levels \> 30%, or new extrapulmonary organ involvement requiring treatment intensification.
Time frame: Day 1 through Month 12
Disease Activity Flares - Behçet's Syndrome
Behçet's Syndrome: Based on the Behçet's Disease Current Activity Form simplified version (BDCAF-s), considering recurrence of oral or genital ulcers, new ocular inflammation, vascular or neurological involvement, or any increase ≥ 2 points in BDCAF-s global score.
Time frame: Day 1 through Month 12
Plan to share: No
Started Jun 2026 (actual). Primary completion is estimated for Apr 2027, 9 months after the start.
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