Study to Estimate the Burden of Herpes Zoster (HZ) and Post-herpetic Neuralgia (PHN) in Italy

Population Based Surveillance to Estimate the Burden of Herpes Zoster and Post-herpetic Neuralgia in Italy

The purpose of this study is to collect data on the incidence, complications, economic burden and impact on the quality of life in adults aged ≥ 50 years with HZ disease in Italy.

Study Overview

• Status: Completed
• Conditions: Herpes Zoster; Herpes Zoster Vaccine
• Intervention / Treatment: Other: Data collection

Detailed Description

The surveillance/recruitment period will take approximately 2 years and once the enrolment of HZ patients has ended, the study will continue for a maximum of 9 months to allow for completion of the follow-up of potential PHN cases.

The data will be captured at protocol specified time-points based on the time of enrolment of each subject.

• Study Type: Observational
• Enrollment (Actual): 395

Contacts and Locations

Study Locations

• Italy
  • Alessano (LE), Italy
    • GSK Investigational Site
  • Rome, Italy, 00144
    • GSK Investigational Site
  • Campania
    • Napoli, Campania, Italy, 80125
      • GSK Investigational Site
    • Napoli, Campania, Italy, 80126
      • GSK Investigational Site
  • Lazio
    • Roma, Lazio, Italy, 00144
      • GSK Investigational Site
    • Roma, Lazio, Italy, 00141
      • GSK Investigational Site
    • Roma, Lazio, Italy, 00142
      • GSK Investigational Site
    • Roma, Lazio, Italy, 00162
      • GSK Investigational Site
    • Roma, Lazio, Italy, 00176
      • GSK Investigational Site
    • Roma, Lazio, Italy, 00197
      • GSK Investigational Site
  • Lombardia
    • Angera (VA), Lombardia, Italy
      • GSK Investigational Site
    • Arcisate (VA), Lombardia, Italy, 21051
      • GSK Investigational Site
    • Comerio (VA), Lombardia, Italy, 21020
      • GSK Investigational Site
    • Fagnano Olona (VA), Lombardia, Italy, 21054
      • GSK Investigational Site
    • Ghirla Valganna (VA), Lombardia, Italy, 21030
      • GSK Investigational Site
    • Induno Olona (VA), Lombardia, Italy, 21040
      • GSK Investigational Site
    • Sesto Calende (VA), Lombardia, Italy, 21018
      • GSK Investigational Site
    • Solbiate Olona (VA), Lombardia, Italy, 21052
      • GSK Investigational Site
    • Varese, Lombardia, Italy, 21100
      • GSK Investigational Site
  • Piemonte
    • Alessandria, Piemonte, Italy, 15121
      • GSK Investigational Site
    • Frugarolo (AL), Piemonte, Italy, 15065
      • GSK Investigational Site
    • Oviglio (AL), Piemonte, Italy, 15026
      • GSK Investigational Site
    • Sale (AL), Piemonte, Italy, 15045
      • GSK Investigational Site
    • Villalvernia (AL), Piemonte, Italy, 15050
      • GSK Investigational Site
  • Puglia
    • Cavallino (LE), Puglia, Italy, 73020
      • GSK Investigational Site
    • Copertino (LE), Puglia, Italy, 73043
      • GSK Investigational Site
    • Cutrofiano (LE), Puglia, Italy, 73020
      • GSK Investigational Site
    • Galatina (LE), Puglia, Italy, 73013
      • GSK Investigational Site
    • Montesano S. (LE), Puglia, Italy, 73035
      • GSK Investigational Site
    • Parabita (LE), Puglia, Italy, 73052
      • GSK Investigational Site
    • Specchia (LE), Puglia, Italy, 73040
      • GSK Investigational Site
  • Toscana
    • Arcidosso (GR), Toscana, Italy, 58031
      • GSK Investigational Site
    • Arezzo, Toscana, Italy, 52100
      • GSK Investigational Site
    • Civitella Paganico (GR), Toscana, Italy, 58045
      • GSK Investigational Site
    • Follonica (GR), Toscana, Italy, 58022
      • GSK Investigational Site
    • Grosseto, Toscana, Italy, 58100
      • GSK Investigational Site
    • Lucignano (AR), Toscana, Italy, 52046
      • GSK Investigational Site
    • Orbetello (GR), Toscana, Italy, 58015
      • GSK Investigational Site
    • Sassofortino (GR), Toscana, Italy, 58029
      • GSK Investigational Site
  • Umbria
    • Perugia, Umbria, Italy, 06125
      • GSK Investigational Site
    • Perugia, Umbria, Italy, 06126
      • GSK Investigational Site
    • Perugia, Umbria, Italy
      • GSK Investigational Site
    • Ripa (PG), Umbria, Italy, 06134
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adult population, male or female aged ≥ 50 years of age presenting with a HZ episode.

Description

Inclusion Criteria:

• A male or female ≥ 50 years of age at the time of study enrolment presenting with acute HZ.

• HZ diagnosis for this HZ episode:

  • Is his/her first outpatient diagnosis (i.e. initial consultation), OR
  • Took place at another site/centre (e.g. emergency room or Dermatologist/Specialist practice) provided the HZ diagnosis is not more than 7 days before the initial visit for the present study (i.e. secondary consultation).
• Written informed consent obtained from the patient.
• Ability to comply with study procedures.

Exclusion Criteria:

• Patient participating in another clinical study (participation in another observational, non-interventional trial is allowed).

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Herpes Zoster Group; Male or female subjects aged 50 years or above, presenting with a herpes zoster (HZ) episode.	Other: Data collection; HZ/PHN booklet, HZ/PHN file and logbook. HZ/PHN booklet will be completed by the patient and the HZ/PHN file and logbook will be completed by the participating general practitioner.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Incidence Rate of Herpes Zoster (HZ) Cases, by Age and Gender	A case of HZ was defined as new unilateral pain (broadly defined to include allodynia and pruritus) accompanied by unilateral rash and no alternative diagnosis. Age ranges were 50-54, 55-59, 60-64, 65-69, 70-74, 75-79 and greater than or equal to (≥) 80 years. The incidence rate was expressed as the number of HZ cases per (/) 1000 person-years.	Day 0 to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Postherpetic Neuralgia (PHN) Cases Among HZ, Overall	PHN persistence refers to pain occurring or persisting from Day 90 to Day 270 after the rash onset. PHN was assessed via the Zoster Pain Inventory (ZBPI) questionnaire, which includes four pain severity items (worst, least, average, present pain) and seven pain interference items which assess general activity, mood, walking ability, work, relations with others, sleep and enjoyment of life. All of the items are rated on an 11-point Likert scale (0-10). For the severity items, 0 = 'no pain' and 10 = 'pain as bad as you can imagine', whereas for the interference items, 0 = 'does not interfere' and 10 = 'completely interferes'.	At Day 90, 180 and 270 after onset of HZ
General Medical History of Cases With HZ, Overall	General medical history focused on characteristics such as patient pre-existing condition and diseases (local trauma, diabetes mellitus, liver disease, alcoholism, renal failure/dialysis, emotional problems, stress or depression, blood malignancy, solid malignancy, hematopoetic cell/ bone marrow transplant, solid organ transplantation, HIV infection, hepatitis C under active therapy, autoimmune disease active and under therapy, other).	Between Day 0 and Day 270.
Other General Medical History Characteristics for HZ Cases, Overall	Other general medical history characteristics referred to arterial problems, cerebral problems, gastric problems, gastric problems, prostate problems (arterial hypertension and allergic rhinitis, arterial hypertension and pacemaker, arteriopathy and past nun-Hodgkin lymphoma, atrial fibrillation, bronchopathy, cerebral thrombosis, cholecyst, chronic cerebral ischemia, chronic leukemia, chronic obstructive pulmonary disease, epilepsy, gastric lymphoma, gastropathy, hypertension, hypertension and hypothyroidism after surgery, hypertension dyslipidemia and hyperthyroidism, hypothyroidism hypertension, polycythaemia, polycythaemia from 10 years, prostate neoplasm, prostate oral anticoagulant therapy cardiopathy, prostatic cancer, right feet arthralgia, thrombocytopenia, vasculopathy chronic brain).	Between Day 0 and Day 270.
Clinical Information of Cases With HZ, Overall	Clinical information of HZ cases referred to experience of any symptoms before rash, actual symptoms before rash (SBR), any complications at initial visit.	Between Day 0 and Day 270
Complications Related to HZ Cases, Overall	HZ related complications refer to cutaneous complications (Varicella Zoster Virus [VZV] dissemination, Bacterial superinfection), ocular (Loss of corneal sensation, Keratitis, Scleritis, Uveitis, Iridocyclitis), neurological (Meningo-encephalitis, Cranial nerve palsies, Peripheral nerve palsies, Ramsay-Hunt syndrome, Persistent HZ-related Pain), visceral [Neural extension of VZV infection (bronchitis, esophagitis,cystitis), VZV dissemination (pneumonia, arthritis, hepatitis] and other.	Between Day 0 and Day 270
Other Complications Related to HZ Cases, Overall	HZ related other complications refer to axillary lympagenopathy, burning sensation, hypoacusis, itching and rectum pain.	Between Day 0 and Day 270
Direct Medical Costs, Direct Non-medical Costs and Indirect Costs	Cost data related to HZ included medication, procedures and referral to hospital/specialist for direct medical costs, transport for direct non-medical costs and missed time from work, sick certificate for the indirect costs.	Up to Day 90
Worst Pain Assessment in HZ Subjects	The ZBPI is an assessment tool in the form of a questionnaire completed by the patient that is specifically designed to assess HZ-associated pain and discomfort. the ZBPI includes four pain severity items (worst, least, average, present pain) and seven pain interference items which assess general activity, mood, walking ability, work, relations with others, sleep and enjoyment of life. All of the items are rated on an 11-point Likert scale (0-10). For the severity items, 0 = 'no pain' and 10 = 'pain as bad as you can imagine', whereas for the interference items, 0 = 'does not interfere' and 10 = 'completely interferes'. Note: The Day 90 window included assessments between Day 83 and Day 97 relative to day of rash onset.	At Day 90
Average Pain Assessment in HZ Subjects	The ZBPI is an assessment tool in the form of a questionnaire completed by the patient that is specifically designed to assess HZ-associated pain and discomfort. the ZBPI includes four pain severity items (worst, least, average, present pain) and seven pain interference items which assess general activity, mood, walking ability, work, relations with others, sleep and enjoyment of life. All of the items are rated on an 11-point Likert scale (0-10). For the severity items, 0 = 'no pain' and 10 = 'pain as bad as you can imagine', whereas for the interference items, 0 = 'does not interfere' and 10 = 'completely interferes'. Note: The Day 90 window included assessments between Day 83 and Day 97 relative to day of rash onset.	At Day 90
Impact of HZ on Quality of Life as Assessed by the Zoster Pain Inventory	PHN persistence refers to pain occurring or persisting between 90-270 days after the rash onset. PHN was assessed via the Zoster Pain Inventory (ZBPI) questionnaire, which includes four pain severity items (worst, least, average, present pain) and seven pain interference items which assess general activity, mood, walking ability, work, relations with others, sleep and enjoyment of life. All of the items are rated on an 11-point Likert scale (0-10). For the severity items, 0 = 'no pain' and 10 = 'pain as bad as you can imagine', whereas for the interference items, 0 = 'does not interfere' and 10 = 'completely interferes'.	At Day 0, 15, 30, 60, 90
Impact of HZ on Quality of Life as Assessed by the EuroQoL-Five Digits	EuroQoL-Five Digits (EQ-5D) is a standardised instrument for use as a measure of health outcome and is designed for self-completion by respondents. Its current format is 3-level and 5 dimensional (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). The EQ-5D index was derived from the ratings recorded every 3 months for each of the five individual items (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). The EQ-5D index/scale goes from 0 (worst health state) to 1 (perfect health state).	At Day 0, 15, 30, 60, 90
PHN Direct Medical Costs, Direct Non-medical Costs and Indirect Costs by Payer/Societal Perspective	Cost data related to HZ included medication, procedures and referral to hospital/specialist for direct medical costs, transport for direct non-medical costs and missed time from work, sick certificate for the indirect costs.	Between Day 90 and Day 270
Worst Pain Assessment in PHN Subjects	The ZBPI is an assessment tool in the form of a questionnaire completed by the patient that is specifically designed to assess HZ-associated pain and discomfort. the ZBPI includes four pain severity items (worst, least, average, present pain) and seven pain interference items which assess general activity, mood, walking ability, work, relations with others, sleep and enjoyment of life. All of the items are rated on an 11-point Likert scale (0-10). For the severity items, 0 = 'no pain' and 10 = 'pain as bad as you can imagine', whereas for the interference items, 0 = 'does not interfere' and 10 = 'completely interferes'. Note: The Day 90 window included assessments between Day 83 and Day 97 relative to day of rash onset.	At Day 90
Average Pain Assessment in PHN Subjects	The ZBPI is an assessment tool in the form of a questionnaire completed by the patient that is specifically designed to assess HZ-associated pain and discomfort. The ZBPI includes four pain severity items (worst, least, average, present pain) and seven pain interference items which assess general activity, mood, walking ability, work, relations with others, sleep and enjoyment of life. All of the items are rated on an 11-point Likert scale (0-10). For the severity items, 0 = 'no pain' and 10 = 'pain as bad as you can imagine', whereas for the interference items, 0 = 'does not interfere' and 10 = 'completely interferes'. Note: The Day 90 window included assessments between Day 83 and Day 97 relative to day of rash onset.	At Day 90
Impact of PHN on Quality of Life as Assessed by the Zoster Pain Inventory	PHN persistence refers to pain occurring or persisting between 90-270 days after the rash onset. PHN was assessed via the Zoster Pain Inventory (ZBPI) questionnaire, which includes four pain severity items (worst, least, average, present pain) and seven pain interference items which assess general activity, mood, walking ability, work, relations with others, sleep and enjoyment of life. All of the items are rated on an 11-point Likert scale (0-10). For the severity items, 0 = 'no pain' and 10 = 'pain as bad as you can imagine', whereas for the interference items, 0 = 'does not interfere' and 10 = 'completely interferes'.	At Day 0, 15, 30, 60, 90
Impact of PHN on Quality of Life as Assessed by the EuroQoL-Five Digits	EuroQoL-Five Digits (EQ-5D) is a standardised instrument for use as a measure of health outcome and is designed for self-completion by respondents. Its current format is 3-level and 5 dimensional (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). The EQ-5D index was derived from the ratings recorded every 3 months for each of the five individual items (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). The EQ-5D index was 0 (worst health state) to 1 (best health state).	At Day 0, 15, 30, 60, 90

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Salvetti A, Ferrari V, Garofalo R, Gazzaniga P, Guerroni A, Metrucci A, Sessa A, Severi ML, Nati G, Ruggeri M, Rossi A, Cappellari L, Gopala K, Tosatto R, Simone B. Incidence of herpes zoster and postherpetic neuralgia in Italian adults aged >/=50 years: A prospective study. Prev Med Rep. 2019 Apr 24;14:100882. doi: 10.1016/j.pmedr.2019.100882. eCollection 2019 Jun.
• Matthews S, De Maria A, Passamonti M, Ristori G, Loiacono I, Puggina A, Curran D. The Economic Burden and Impact on Quality of Life of Herpes Zoster and Postherpetic Neuralgia in Individuals Aged 50 Years or Older in Italy. Open Forum Infect Dis. 2019 Jan 12;6(2):ofz007. doi: 10.1093/ofid/ofz007. eCollection 2019 Feb.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 26, 2013
• Primary Completion (ACTUAL): October 5, 2016
• Study Completion (ACTUAL): October 5, 2016

Study Registration Dates

• First Submitted: January 17, 2013
• First Submitted That Met QC Criteria: January 17, 2013
• First Posted (ESTIMATE): January 21, 2013

Study Record Updates

• Last Update Posted (ACTUAL): May 22, 2020
• Last Update Submitted That Met QC Criteria: May 8, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Quality of life; Adults; Burden; Incidence; Complications; Surveillance; Herpes Zoster; Cost; Italy
• Additional Relevant MeSH Terms: Nervous System Diseases; Skin Diseases; Virus Diseases; Infections; Pain; Neurologic Manifestations; Neuromuscular Diseases; Peripheral Nervous System Diseases; DNA Virus Infections; Skin Diseases, Infectious; Skin Diseases, Viral; Herpesviridae Infections; Varicella Zoster Virus Infection; Neuralgia; Herpes Zoster; Herpes Simplex; Neuralgia, Postherpetic
• Other Study ID Numbers: 116208

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR