Autoimmune Rheumatic DiseasesPhase 4PRoHerpARDNCT07341386
Prevention of Recurrence of Herpes Simplex in Autoimmune Rheumatic Diseases
A Phase 4 study testing Acyclovir (ACV) in people with Autoimmune Rheumatic Diseases and Recurrent Herpes Simplex, run by University of Sao Paulo General Hospital at 1 site in Brazil.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Autoimmune Rheumatic Diseases, Recurrent Herpes Simplex, Prevention
- What is being tested?
- Acyclovir (ACV)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 62 participants
- Where
- 1 siteBrazil
- Study dates
- 25 Jun 2026to 1 Apr 2028
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- -Participants will be excluded if they have a known hypersensitivity to acyclovir or any component of the study medication.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Brazil1 site, 1 recruiting
- Recruiting
Reumatology division of Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Sao Paulo 05403-000
São Paulo, São Paulo, 05403-000
Eloisa Bomfa, Md, PhD, +55 11 30617490, eloisa.bomfa@hc.fm.usp.br
About this study
Official title: Prevention of Recurrence of Herpes Simplex in Patients With Autoimmune Rheumatic Diseases
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:
Read more
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.
Read the detailed description
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.
- Being tested
- Acyclovir (ACV), Placebo
- Keywords
- Herpes Simplex Virus, Acyclovir, Autoimmune Rheumatic Diseases, Rheumatology, Pediatric Rheumatology, Antiviral Suppressive Therapy, Infectious Disease Prevention
- Medical subject headings
- Herpes Simplex
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
PlaceboOther
Matching oral placebo, administered twice a day for 12 months.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to Month 24
Secondary outcomes (18)
Safety Profile - Adverse Events (AEs)
Frequency and severity of adverse events (e.g., gastrointestinal discomfort, headache, rash) reported during the 12-month treatment phase.
Measured: 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.
Measured: Day 1 through Month 12
Treatment Discontinuation Due to AEs
Proportion of participants who discontinue acyclovir or placebo due to adverse events.
Measured: Day 1 through Month 12
Time to First HSV Reactivation
Number of days from randomization to first documented HSV reactivation.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: Day 1 through Month 12
Disease Activity Flares - Ankylosing Spondylitis
Ankylosing Spondylitis (AS): An increase in Ankylosing Spondylitis Disease Activity Score (ASDAS) > 0.9.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Day 1 through Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2026
- Study start25 Jun 2026
- Primary completion1 Apr 2027 (estimated)
- Study completion1 Apr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Autoimmune Rheumatic DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 62 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Sao Paulo General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07341386
- Sponsor's protocol ID
- 87204225.7.0000.0068
- Acronym
- PRoHerpARD
- Status last verified
- Oct 2025
- First submitted
- 5 Jan 2026
- Last updated
- 5 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 9697714Fatahzadeh 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.
PubMed 17939933Beyar-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.
PubMed 31536817