Prevention of Recurrence of Herpes Simplex in Autoimmune Rheumatic Diseases

NCT07341386 | Not Yet Recruiting Phase 4

• 1 other identifier: 87204225.7.0000.0068
• Study Type: interventional
• Target: 62
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Autoimmune Rheumatic Diseases; Recurrent Herpes Simplex; Prevention

Keywords

Herpes Simplex Virus; Acyclovir; Autoimmune Rheumatic Diseases; Rheumatology; Pediatric Rheumatology; Antiviral Suppressive Therapy; Infectious Disease Prevention

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline to Month 24

Secondary Outcomes (18)

• Safety Profile - Adverse Events (AEs)

  Day 1 through Month 12

• Frequency of Serious Adverse Events (SAEs)

  Day 1 through Month 12

• Treatment Discontinuation Due to AEs

  Day 1 through Month 12

• Time to First HSV Reactivation

  Day 1 through Month 12

• Factors Associated with HSV Reactivation

  Day 1 through Month 24

Study Arms (2)

ACV

ACTIVE COMPARATOR

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)

Placebo

PLACEBO COMPARATOR

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

Interventions

Acyclovir (ACV) DRUG

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.

ACV

Placebo OTHER

Matching oral placebo, administered twice a day for 12 months.

Placebo

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Eligible participants must be \>12 years old
• Any sex
• Have a confirmed diagnosis of an autoimmune rheumatic disease (ARD) based on internationally accepted classification criteria, including: rheumatoid arthritis (ACR/EULAR 2010), juvenile idiopathic arthritis (ILAR), axial spondyloarthritis (ASAS 2009), psoriatic arthritis (CASPAR 2012), systemic lupus erythematosus (SLICC 2012), systemic sclerosis (ACR 2013), dermatomyositis/polymyositis (Bohan \& Peter), systemic vasculitis (Takayasu arteritis, granulomatosis with polyangiitis, polyarteritis nodosa), primary Sjögren's syndrome (ACR/EULAR 2016), mixed connective tissue disease (Alarcón-Segovia or Kasukawa criteria), chronic recurrent multifocal osteomyelitis (Jansson et al., 2007), sarcoidosis (ATS/ERS/WASOG 2020 statement) and behçet's syndrome (International Study Group, 1990).
• Present serologic evidence of prior HSV infection (complement fixation titer ≥ 1:8)
• A clinical history of recurrent oral or genital herpes simplex virus infection, defined as at least four episodes in the past 12 months.

You may not qualify if:

• Participants will be excluded if they have a known hypersensitivity to acyclovir or any component of the study medication.

Sponsors & Collaborators

• University of Sao Paulo General Hospital: lead
• Fundação de Amparo à Pesquisa do Estado de São Paulo: collaborator

Related Publications (3)

• Ioannidis JP, Collier AC, Cooper DA, Corey L, Fiddian AP, Gazzard BG, Griffiths PD, Contopoulos-Ioannidis DG, Lau J, Pavia AT, Saag MS, Spruance SL, Youle MS. Clinical efficacy of high-dose acyclovir in patients with human immunodeficiency virus infection: a meta-analysis of randomized individual patient data. J Infect Dis. 1998 Aug;178(2):349-59. doi: 10.1086/515621.

  PMID: 9697714 BACKGROUND

• Fatahzadeh M, Schwartz RA. Human herpes simplex virus infections: epidemiology, pathogenesis, symptomatology, diagnosis, and management. J Am Acad Dermatol. 2007 Nov;57(5):737-63; quiz 764-6. doi: 10.1016/j.jaad.2007.06.027.

  PMID: 17939933 BACKGROUND

• Beyar-Katz O, Bitterman R, Zuckerman T, Ofran Y, Yahav D, Paul M. Anti-herpesvirus prophylaxis, pre-emptive treatment or no treatment in adults undergoing allogeneic transplant for haematological disease: systematic review and meta-analysis. Clin Microbiol Infect. 2020 Feb;26(2):189-198. doi: 10.1016/j.cmi.2019.09.003. Epub 2019 Sep 16.

  PMID: 31536817 BACKGROUND

MeSH Terms

Conditions

Herpes Simplex

Interventions

Acyclovir

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Skin Diseases, Viral; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Central Study Contacts

Eloisa Bonfá Full Professor

CONTACT

(11) 3061-7492; reumatologia.fmusp@hc.fm.usp.br

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2026
• First Posted: January 14, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2028
• Last Updated: March 5, 2026

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share