COPDPhase 2EViSCONCT03699904
Epstein-Barr Virus Suppression in Chronic Obstructive Pulmonary Disease (EViSCO): a Phase 2 Randomised Control Trial
A Phase 2 study testing Valaciclovir in people with COPD and EBV, run by Belfast Health and Social Care Trust at 1 site in United Kingdom.
Trial summary
COPD is a major public health problem and will shortly become the third most common cause of global mortality. There are currently no treatments that can meaningfully alter the progression of COPD or the time to death. Consequently novel therapeutic strategies for COPD are urgently required. Read more about this study
- Who is it for?
- Ages 18 years and older
- What is being tested?
- Valaciclovir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 85 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 11 Oct 2018to 1 Jul 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age over 18 years.
- Clinical diagnosis of COPD as defined by the Global Initiative for Chronic Obstructive Lung Disease criteria (FEV1/FVC <70%) with GOLD 2 and GOLD 3 airflow obstruction (FEV1 30-80% predicted) with significant symptoms.
- Presence of Epstein-Barr virus on sputum PCR analysis.
Who cannot join
- Respiratory failure (defined as long-term oxygen therapy).
- An acute exacerbation of COPD in the previous month (defined as an acute, sustained worsening of symptoms that is beyond normal day-to-day variations).
- A diagnosis of asthma.
- Patients with known hypersensitivity to valaciclovir or aciclovir.
- Patients unable to swallow study drug capsules.
- Established diffuse interstitial lung disease (e.g. Idiopathic Pulmonary Fibrosis).
Show all 13Show fewer
- Established diagnosis of symptomatic bronchiectasis.
- Patients known to be pregnant or breastfeeding.
- Patients with an estimated creatinine clearance less than 50ml/minute.
- Known participation in investigational medicinal product trials within 30 days.
- Patients who do not adequately understand verbal or written information.
- Concomitant use of nephrotoxic medicinal products or medicines associated with altered renal tubular secretion. These include aminoglycosides, organoplatinum compounds, methotrexate, pentamidine, foscarnet, ciclosporin, tacrolimus,tenofovir, cimetidine and probenecid. As iodinated contrast used in radiological examinations can be nephrotoxicity patients with planned radiological contrast studies will be deferred for a reasonable time until after their contrast.
- For the exploratory bronchoscopy sub-study patients will require adequate oxygen saturations, FEV1 >0.5 L and will not be performed while patients are taking aspirin or clopidogrel (BTS guidelines 2013).
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Belfast Health and Social Care Trust
Belfast, Down, BT5 7GX
About this study
Official title: A Randomised, Double-blind, Placebo-controlled Trial to Evaluate the Effect of Epstein-Barr Virus Suppression in Chronic Obstructive Pulmonary Disease (EViSCO).
COPD is a major public health problem and will shortly become the third most common cause of global mortality. There are currently no treatments that can meaningfully alter the progression of COPD or the time to death. Consequently novel therapeutic strategies for COPD are urgently required. This will be a randomised, double-blind, placebo-controlled, trial of Epstein-Barr virus suppression in COPD. Participants will be randomised to receive valaciclovir 1 gram three times daily for 8 weeks or matching placebo. The study will measure EBV suppression using quantitative PCR. Secondary outcomes will include Lung function quality of life and drug tolerability. The exploratory analysis will evaluate biomarkers of airway inflammation within the sputum and blood.
Read the detailed description
The study will evaluate the role of antiviral therapy in COPD. Previous research has demonstrated that Epstein-Barr virus (EBV) is more frequently identified in the airways of COPD sufferers when compared to unaffected smokers. It is not known whether suppression of EBV helps in COPD.
Hypothesis. The primary hypothesis is that treatment with valaciclovir is safe and will suppress Epstein-Barr virus in the sputum of patients with COPD.
Trial objectives. To conduct a randomised, double-blind, placebo-controlled, trial of Epstein-Barr virus suppression in COPD.
To evaluate the safety of valaciclovir (1 gram three times daily for 8 weeks) for the suppression of Epstein-Barr virus in COPD.
To study the biological effects of EBV suppression on airway and blood markers of inflammation in COPD.
The investigators will conduct a clinical trial to evaluate if a long established antiviral therapy (valaciclovir), routinely used to treat herpes zoster virus infection, can be used to suppress EBV shedding within the airways of COPD sufferers compared to placebo. The treatment will be randomised and blinded to both patients and investigators. The trial will recruit 88 participants who will undergo lung function testing, clinical assessment and provide blood and sputum samples at three separate hospital visits during an 8-week period (samples will be collected at 0, 4 \& 8 weeks). A small subgroup of trial participants will undergo bronchoscopy on a voluntary basis to enable assessment of the airway cells before and after treatment. The study will take place in The Belfast Health and Social Care Trust. Patients who suffer from COPD (GOLD 2 \& GOLD 3) and concurrent EBV infection will be eligible to participate in the study. If the treatment is effective this will lead to further research to determine whether antiviral therapy is effective in patients with COPD. The study will also provide new information about the mechanisms of how COPD develops and potentially identify new therapeutic targets.
Data management. The Northern Ireland Clinical Trials Unit (NICTU) will be responsible for data management during the conduct of the trial. Following electronic CRF submission data will be processed by NICTU as per CTU SOPs. All data will be anonymised. Data queries will be generated by site staff as required to clarify data or request missing information.
Data storage. All data and trial records will be stored by the CI in accordance with current regulatory requirements.
Sample size. A sample size of 31 subjects per group will have a 90% power at a two-tailed significance level of 0.05 to detect a difference in the exploratory efficacy outcome (EBV quantitative PCR).
Statistical analysis. Analyses will be on an intention-to-treat basis and all statistical tests will be at the 2-sided p-value of 0.05. Comparison between groups for the primary outcome measure SARs will be made using Fisher's exact test.
The exploratory efficacy outcome EBV shedding will initially be analyzed by chi-square test followed by logistic regression with adjustment for covariates if required. The comparison of continuous secondary/exploratory outcomes will be initially by t-tests followed by analysis of covariance if adjustment for covariates is required. Statistical diagnostic methods will be used to check for violations of the assumptions, and transformations will be performed where required.
Correlations between changes in the biological markers measured and physiological and clinical outcomes will be assessed by appropriate graphical and statistical methods including Pearson's (or Spearman's) correlation coefficient.
A single final analysis is planned at the end of the trial.
A detailed statistical analysis plan will be written before the statistical analysis commences.
- Being tested
- Valaciclovir, Placebo capsules (containing Avicel blend)
- Keywords
- COPD, EBV
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ValaciclovirDrug
Participants will self-administer Valaciclovir 1 gram three times daily for 8 weeks.
Placebo capsules (containing Avicel blend)Drug
Participants will self-administer two matching placebo capsules (containing Avicel blend) three times daily for 8 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Active arm | Experimental | Valaciclovir 1 gram orally three times daily for 8 weeks. Receives: Drug: Valaciclovir |
| Placebo arm | Placebo comparator | Matching placebo capsules (containing Avicel blend). Two capsules three times daily for 8 weeks. Receives: Drug: Placebo capsules (containing Avicel blend) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Serious Adverse Reactions (SARs)
The primary outcome measure will be drug safety of valaciclovir (1 gram three times daily for 8 weeks) as defined by the incidence of Serious Adverse Reactions (SARs).
Measured: Up to 28 days after completion of the study drug
EBV viral load
The primary efficacy outcome is suppression of Epstein-Barr virus in the sputum measured using quantitative PCR at baseline and 8 weeks.
Measured: Change from baseline to 8 weeks.
Secondary outcomes (2)
Forced expiratory volume in 1 second (FEV1)
Lung function measured by spirometry, the principal component will be the change in FEV1 from baseline to week 8.
Measured: Change from baseline to 8 weeks
Drug tolerability as measured by the proportion of tablets self-administered.
Drug tolerability will be measured by total number of tablets self-administered as a proportion of total number of tablets supplied.
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2018
- Study start11 Oct 2018
- Primary completion7 May 2020
- Study completion1 Jul 2020
Why it stopped: In light of the evolving Covid19 pandemic ongoing study recruitment was felt to pose an unacceptable risk to patient safety.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for COPDStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Parallel assignment.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 85 participants (actual)
Sponsor and investigators
- Lead sponsor
- Belfast Health and Social Care Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Northern Ireland Clinical Trials Unit, Queen's University, Belfast
- Responsible party
- Sponsor
- Investigators
- Joe Kidney, MB, MD, Principal investigator, Belfast Health and Social Care Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03699904
- Sponsor's protocol ID
- 14143JK-AS
- Acronym
- EViSCO
- Status last verified
- Sep 2020
- First submitted
- 1 Oct 2018
- Last updated
- 30 Sep 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Linden DA, Guo-Parke H, McKelvey MC, Einarsson GG, Lee AJ, Fairley DJ, Brown V, Lundy G, Campbell C, Logan D, McFarland M, Singh D, McAuley DF, Taggart CC, Kidney JC. Valaciclovir for Epstein-Barr Virus Suppression in Moderate-to-Severe COPD: A Randomized Double-Blind Placebo-Controlled Trial. Chest. 2023 Sep;164(3):625-636. doi: 10.1016/j.chest.2023.03.040. Epub 2023 Apr 1.
PubMed 37011709
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Double-blind, Placebo-controlled Trial to Evaluate the Effect of Epstein-Barr Virus Suppression in Chronic Obstructive Pulmonary Disease (EViSCO).
- ClinicalTrials.gov ID
- NCT03699904
- Acronym / sponsor ID
- EViSCO / 14143JK-AS
- Keywords
- COPD, EBV
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: In light of the evolving Covid19 pandemic ongoing study recruitment was felt to pose an unacceptable risk to patient safety.
- Enrolment
- 85 participants (actual)
- Lead sponsor
- Belfast Health and Social Care TrustUniversity, hospital or other
- Collaborators
- Northern Ireland Clinical Trials Unit, Queen's University, Belfast
- Study start
- 11 Oct 2018 (actual)
- Primary completion
- 7 May 2020 (actual)
- Study completion
- 1 Jul 2020 (actual)
- First posted
- 9 Oct 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
COPD is a major public health problem and will shortly become the third most common cause of global mortality. There are currently no treatments that can meaningfully alter the progression of COPD or the time to death. Consequently novel therapeutic strategies for COPD are urgently required. This will be a randomised, double-blind, placebo-controlled, trial of Epstein-Barr virus suppression in COPD. Participants will be randomised to receive valaciclovir 1 gram three times daily for 8 weeks or matching placebo. The study will measure EBV suppression using quantitative PCR. Secondary outcomes will include Lung function quality of life and drug tolerability. The exploratory analysis will evaluate biomarkers of airway inflammation within the sputum and blood.
Detailed description
The study will evaluate the role of antiviral therapy in COPD. Previous research has demonstrated that Epstein-Barr virus (EBV) is more frequently identified in the airways of COPD sufferers when compared to unaffected smokers. It is not known whether suppression of EBV helps in COPD.
Hypothesis. The primary hypothesis is that treatment with valaciclovir is safe and will suppress Epstein-Barr virus in the sputum of patients with COPD.
Trial objectives. To conduct a randomised, double-blind, placebo-controlled, trial of Epstein-Barr virus suppression in COPD.
To evaluate the safety of valaciclovir (1 gram three times daily for 8 weeks) for the suppression of Epstein-Barr virus in COPD.
To study the biological effects of EBV suppression on airway and blood markers of inflammation in COPD.
The investigators will conduct a clinical trial to evaluate if a long established antiviral therapy (valaciclovir), routinely used to treat herpes zoster virus infection, can be used to suppress EBV shedding within the airways of COPD sufferers compared to placebo. The treatment will be randomised and blinded to both patients and investigators. The trial will recruit 88 participants who will undergo lung function testing, clinical assessment and provide blood and sputum samples at three separate hospital visits during an 8-week period (samples will be collected at 0, 4 \& 8 weeks). A small subgroup of trial participants will undergo bronchoscopy on a voluntary basis to enable assessment of the airway cells before and after treatment. The study will take place in The Belfast Health and Social Care Trust. Patients who suffer from COPD (GOLD 2 \& GOLD 3) and concurrent EBV infection will be eligible to participate in the study. If the treatment is effective this will lead to further research to determine whether antiviral therapy is effective in patients with COPD. The study will also provide new information about the mechanisms of how COPD develops and potentially identify new therapeutic targets.
Data management. The Northern Ireland Clinical Trials Unit (NICTU) will be responsible for data management during the conduct of the trial. Following electronic CRF submission data will be processed by NICTU as per CTU SOPs. All data will be anonymised. Data queries will be generated by site staff as required to clarify data or request missing information.
Data storage. All data and trial records will be stored by the CI in accordance with current regulatory requirements.
Sample size. A sample size of 31 subjects per group will have a 90% power at a two-tailed significance level of 0.05 to detect a difference in the exploratory efficacy outcome (EBV quantitative PCR).
Statistical analysis. Analyses will be on an intention-to-treat basis and all statistical tests will be at the 2-sided p-value of 0.05. Comparison between groups for the primary outcome measure SARs will be made using Fisher's exact test.
The exploratory efficacy outcome EBV shedding will initially be analyzed by chi-square test followed by logistic regression with adjustment for covariates if required. The comparison of continuous secondary/exploratory outcomes will be initially by t-tests followed by analysis of covariance if adjustment for covariates is required. Statistical diagnostic methods will be used to check for violations of the assumptions, and transformations will be performed where required.
Correlations between changes in the biological markers measured and physiological and clinical outcomes will be assessed by appropriate graphical and statistical methods including Pearson's (or Spearman's) correlation coefficient.
A single final analysis is planned at the end of the trial.
A detailed statistical analysis plan will be written before the statistical analysis commences.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Parallel assignment.
| Arm | Type | Receives |
|---|---|---|
| Active arm | Experimental | Drug: ValaciclovirValaciclovir 1 gram orally three times daily for 8 weeks. |
| Placebo arm | Placebo comparator | Drug: Placebo capsules (containing Avicel blend)Matching placebo capsules (containing Avicel blend). Two capsules three times daily for 8 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age over 18 years.
- Clinical diagnosis of COPD as defined by the Global Initiative for Chronic Obstructive Lung Disease criteria (FEV1/FVC <70%) with GOLD 2 and GOLD 3 airflow obstruction (FEV1 30-80% predicted) with significant symptoms.
- Presence of Epstein-Barr virus on sputum PCR analysis.
Key exclusion criteria (13 listed)
- Respiratory failure (defined as long-term oxygen therapy).
- An acute exacerbation of COPD in the previous month (defined as an acute, sustained worsening of symptoms that is beyond normal day-to-day variations).
- A diagnosis of asthma.
- Patients with known hypersensitivity to valaciclovir or aciclovir.
- Patients unable to swallow study drug capsules.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ValaciclovirParticipants will self-administer Valaciclovir 1 gram three times daily for 8 weeks. | Drug | Active arm |
| Placebo capsules (containing Avicel blend)Participants will self-administer two matching placebo capsules (containing Avicel blend) three times daily for 8 weeks. | Drug | Placebo arm |
Primary outcome
Incidence of Serious Adverse Reactions (SARs)
Time frame: Up to 28 days after completion of the study drug
The primary outcome measure will be drug safety of valaciclovir (1 gram three times daily for 8 weeks) as defined by the incidence of Serious Adverse Reactions (SARs).
EBV viral load
Time frame: Change from baseline to 8 weeks.
The primary efficacy outcome is suppression of Epstein-Barr virus in the sputum measured using quantitative PCR at baseline and 8 weeks.
2 secondary outcomes
Forced expiratory volume in 1 second (FEV1)
Time frame: Change from baseline to 8 weeks
Drug tolerability as measured by the proportion of tablets self-administered.
Time frame: 8 weeks
Results and safety
The study was stopped early (reason given: In light of the evolving Covid19 pandemic ongoing study recruitment was felt to pose an unacceptable risk to patient safety.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2020.
- Derived from this study: PubMed 37011709Linden DA, Guo-Parke H, McKelvey MC, Einarsson GG, Lee AJ, Fairley DJ, Brown V, Lundy G, Campbell C, Logan D, McFarland M, Singh D, McAuley DF, Taggart CC, Kidney JC. Valaciclovir for Epstein-Barr Virus Suppression in Moderate-to-Severe COPD: A Randomized Double-Blind Placebo-Controlled Trial. Chest. 2023 Sep;164(3):625-636. doi: 10.1016/j.chest.2023.03.040. Epub 2023 Apr 1.
- Individual participant dataSharing planned: Undecided
Related trials for COPD
RecruitingPhase 2
A Study of Brenipatide (LY3537031) in Adult Participants With Moderate-to-Severe Chronic Obstructive Pulmonary Disease (COPD)
Pulmonary Disease, Chronic Obstructive
RecruitingPhase 2
Oral Sildenafil for Exercise Capacity, Dyspnea and Cardiopulmonary Function in COPD
Chronic Obstructive Pulmonary Disease
Recruiting
Evaluating the Safety and Efficacy of dNerva Lung Denervation System in Patients With COPD
COPD, Chronic Obstructive Pulmonary Disease
Recruiting
WIN Ratio Analysis to Determine a Strategy of Non- Invasive SUpport for Respiratory Failure in the EmeRgency Department
Acute Hypoxic Respiratory Failure, Acute Respiratory Distress Syndrome (ARDS)
Recruiting
Comparison of Several Oxygenation Targets With Different Oxygen Interfaces - Impact on Oxygen Flow Rates
Oxygen Toxicity, COPD Bronchitis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joe Kidney, MB, MD principal investigator
Belfast Health and Social Care Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Valaciclovir in people with COPD and EBV, run by Belfast Health and Social Care Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 30 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: In light of the evolving Covid19 pandemic ongoing study recruitment was felt to pose an unacceptable risk to patient safety.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Serious Adverse Reactions (SARs) (time frame: Up to 28 days after completion of the study drug). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03699904, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2020.