Ignite Creation Date:
2024-05-05 @ 11:07 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00007501
Status:
COMPLETED
Last Update Posted:
2013-07-04
First Post:
2000-12-29
Brief Title:
Shingles Prevention Study
Sponsor:
US Department of Veterans Affairs
Organization:
VA Office of Research and Development
Study Overview
Official Title:
CSP 403 - Trial of Varicella Zoster Vaccine for the Prevention of Herpes Zoster and Its Complications
Status:
COMPLETED
Status Verified Date:
2013-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
SPS
Brief Summary:
The incidence and severity of HZ or shingles as well as the frequency and severity of its complications increases markedly with increasing age More than half of all cases occur in persons over the age of 60 Even without complications HZ can interfere with an elderly patients ability to perform essential activities of daily living resulting in a loss of independence that is emotionally devastating and frequently irreversible The most common complication of HZ in elderly persons is postherpetic neuralgia PHN which frequently results in disordered sleep chronic fatigue anxiety and severe depression Antiviral therapy has a modest impact on the acute phase of HZ However it does not appear to prevent the development of PHN
This study is a 55 year randomized double-blind placebo-controlled efficacy trial to determine whether vaccination with live-attenuated OkaMerck varicella-zoster decreases the incidence andor severity of herpes zoster HZ and its complications in adults 60 years of age and older
This study is a 55 year randomized double-blind placebo-controlled efficacy trial to determine whether vaccination with live-attenuated OkaMerck varicella-zoster decreases the incidence andor severity of herpes zoster HZ and its complications in adults 60 years of age and older
Detailed Description:
Primary Hypothesis
Immunization with live attenuated OkaMerck varicella-zoster vaccine will significantly reduce the burden of illness associated with herpes zoster HZ
Secondary Hypotheses
Immunization with live attenuated OkaMerck varicella-zoster vaccine will reduce the incidence of postherpetic neuralgia PHN
Primary Outcomes
The primary outcome is the burden of illness due to HZ defined by the area under the worst pain versus time curve measured during the 6 month period following HZ rash onset in subjects who develop of HZ The burden of illness outcome is sensitive to the incidence severity and duration of HZ-associated pain The secondary outcome is the incidence of PHN where PHN is defined as HZ-associated pain rated as greater than or equal to 3 on a 0 to 10 scale persisting or appearing more than 30 days after the onset of the HZ rash
Interventions
Immunization with 05 ml live attenuated OkaMerck varicella-zoster vaccine versus vaccine placebo
Study Abstract
The incidence and severity of HZ or shingles as well as the frequency and severity of its complications increases markedly with increasing age More than half of all cases occur in persons over the age of 60 Even without complications HZ can interfere with an elderly patients ability to perform essential activities of daily living resulting in a loss of independence that is emotionally devastating and frequently irreversible The most common complication of HZ in elderly persons is postherpetic neuralgia PHN which frequently results in disordered sleep chronic fatigue anxiety and severe depression Antiviral therapy has a modest impact on the acute phase of HZ However it does not appear to prevent the development of PHN
This study was a 55 year randomized double-blind placebo-controlled efficacy trial to determine whether vaccination with live-attenuated OkaMerck varicella-zoster decreases the incidence andor severity of herpes zoster HZ and its complications in adults 60 years of age and older 37200 subjects over 60 years of age will be randomized at 22 sites to receive either vaccine or placebo At least one third of the subjects were to be 70 years of age or older Subjects were followed actively for HZ until at least 750 cases of HZ and at least 62 cases of PHN occurred Subjects who developed HZ were evaluated for severity and duration of associated pain extent and duration of rash and for changes in quality of life associated with the disease for six months after the onset of HZ rash All adverse events serious and non-serious occurring within 42 days after vaccination were recorded Thereafter serious adverse events were recorded if assessed as possibly related to the vaccination An adverse event substudy was to enroll 6000 subjects for recording all adverse events on a vaccination Report Card Substudy participants were also followed for any hospital admissions during the study
The study was initiated in December 1998 Patient recruitment began in November 1998 at one site at 20 sites between February 1999 and July 1999 and at one site that was added in January 2000 On September 26 2001 enrollment in the study was completed with 38456 randomized subjects The time point for the study definition of PHN was changed by protocol amendment from 30 days to 90 days after HZ rash onset A formal sample size re-estimation was performed in June 2003 The Executive Committee and DSMB reviewed these results and approved the increase in event size from 400 to 750 evaluable cases of HZ for the primary endpoint It was projected that the number of evaluable cases of HZ for the primary endpoint and the number of evaluable cases of PHN for the secondary co-primary endpoint would be observed by the end of September 2003 Therefore the Study initiated its closeout plan beginning in October 2004 Follow-up of the last suspected case of HZ was completed in March 2004 and closeout interviews for the more than 37000 surviving subjects were completed as of April 28 2004
The results of the main efficacy and safety analyses were unblinded on December 1 2004 and presented to the DSMB Executive Committee and representatives for Merck Co Inc Letters were sent to the study subjects informing them of the overall results and the treatment they received The main manuscript was published in the New England Journal of Medicine June 2005 3522271-84 The vaccine was approved for the prevention of shingles by the FDA on May 25 2006 The main efficacy study is closed Additionally three substudies have been conducted
A substudy CSP403B was initiated in November 2005 to offer investigational zoster vaccine to the placebo recipients of CSP403 Vaccination was completed in March 2007 with 13681 75 of the placebo recipients vaccinated This substudy is closed The safety results from the substudy were published in the Journal of Infectious Diseases J Infect Dis 2013 May 31 epub
A short-term persistence substudy CSP403A was initiated in September 2004 to extend the follow-up vaccine and placebo recipients to assess the longer term effectiveness of the vaccine This substudy bridged the period between the end of the efficacy study and the vaccination of placebo recipients and the initiation of a long-term persistence study The study enrolled 14270 subjects and completed follow-up in May 2007 This substudy is closed and is in ongoing analysis The primary results for this study were published in Clinical Infectious Diseases Clin Infect Dis 2012 Nov 1555101320-1328
CSP403C the Long-Term Persistence Substudy was initiated in March 2006 and enrolled 6867 vaccine recipients from the main efficacy study Enrollment was restricted to vaccine recipients from the main efficacy study with no history of herpes zoster This study was initiated to complete an additional five-years of follow-up post-vaccination The objective of this study was to estimate the longer-term durability of zoster vaccine efficacy by following a cohort of vaccine recipients from the primary efficacy study for three study outcomes 1 the incidence of herpes zoster 2 the incidence of postherpetic neuralgia PHN and 3 the burden of illness BOI due to herpes zoster The study completed surveillance for new cases of herpes zoster as of December 2010 and completed the follow-up of the last case of herpes zoster in February 2011 All study sites have been closed out This substudy has been completed and is in the final analysis phase
Immunization with live attenuated OkaMerck varicella-zoster vaccine will significantly reduce the burden of illness associated with herpes zoster HZ
Secondary Hypotheses
Immunization with live attenuated OkaMerck varicella-zoster vaccine will reduce the incidence of postherpetic neuralgia PHN
Primary Outcomes
The primary outcome is the burden of illness due to HZ defined by the area under the worst pain versus time curve measured during the 6 month period following HZ rash onset in subjects who develop of HZ The burden of illness outcome is sensitive to the incidence severity and duration of HZ-associated pain The secondary outcome is the incidence of PHN where PHN is defined as HZ-associated pain rated as greater than or equal to 3 on a 0 to 10 scale persisting or appearing more than 30 days after the onset of the HZ rash
Interventions
Immunization with 05 ml live attenuated OkaMerck varicella-zoster vaccine versus vaccine placebo
Study Abstract
The incidence and severity of HZ or shingles as well as the frequency and severity of its complications increases markedly with increasing age More than half of all cases occur in persons over the age of 60 Even without complications HZ can interfere with an elderly patients ability to perform essential activities of daily living resulting in a loss of independence that is emotionally devastating and frequently irreversible The most common complication of HZ in elderly persons is postherpetic neuralgia PHN which frequently results in disordered sleep chronic fatigue anxiety and severe depression Antiviral therapy has a modest impact on the acute phase of HZ However it does not appear to prevent the development of PHN
This study was a 55 year randomized double-blind placebo-controlled efficacy trial to determine whether vaccination with live-attenuated OkaMerck varicella-zoster decreases the incidence andor severity of herpes zoster HZ and its complications in adults 60 years of age and older 37200 subjects over 60 years of age will be randomized at 22 sites to receive either vaccine or placebo At least one third of the subjects were to be 70 years of age or older Subjects were followed actively for HZ until at least 750 cases of HZ and at least 62 cases of PHN occurred Subjects who developed HZ were evaluated for severity and duration of associated pain extent and duration of rash and for changes in quality of life associated with the disease for six months after the onset of HZ rash All adverse events serious and non-serious occurring within 42 days after vaccination were recorded Thereafter serious adverse events were recorded if assessed as possibly related to the vaccination An adverse event substudy was to enroll 6000 subjects for recording all adverse events on a vaccination Report Card Substudy participants were also followed for any hospital admissions during the study
The study was initiated in December 1998 Patient recruitment began in November 1998 at one site at 20 sites between February 1999 and July 1999 and at one site that was added in January 2000 On September 26 2001 enrollment in the study was completed with 38456 randomized subjects The time point for the study definition of PHN was changed by protocol amendment from 30 days to 90 days after HZ rash onset A formal sample size re-estimation was performed in June 2003 The Executive Committee and DSMB reviewed these results and approved the increase in event size from 400 to 750 evaluable cases of HZ for the primary endpoint It was projected that the number of evaluable cases of HZ for the primary endpoint and the number of evaluable cases of PHN for the secondary co-primary endpoint would be observed by the end of September 2003 Therefore the Study initiated its closeout plan beginning in October 2004 Follow-up of the last suspected case of HZ was completed in March 2004 and closeout interviews for the more than 37000 surviving subjects were completed as of April 28 2004
The results of the main efficacy and safety analyses were unblinded on December 1 2004 and presented to the DSMB Executive Committee and representatives for Merck Co Inc Letters were sent to the study subjects informing them of the overall results and the treatment they received The main manuscript was published in the New England Journal of Medicine June 2005 3522271-84 The vaccine was approved for the prevention of shingles by the FDA on May 25 2006 The main efficacy study is closed Additionally three substudies have been conducted
A substudy CSP403B was initiated in November 2005 to offer investigational zoster vaccine to the placebo recipients of CSP403 Vaccination was completed in March 2007 with 13681 75 of the placebo recipients vaccinated This substudy is closed The safety results from the substudy were published in the Journal of Infectious Diseases J Infect Dis 2013 May 31 epub
A short-term persistence substudy CSP403A was initiated in September 2004 to extend the follow-up vaccine and placebo recipients to assess the longer term effectiveness of the vaccine This substudy bridged the period between the end of the efficacy study and the vaccination of placebo recipients and the initiation of a long-term persistence study The study enrolled 14270 subjects and completed follow-up in May 2007 This substudy is closed and is in ongoing analysis The primary results for this study were published in Clinical Infectious Diseases Clin Infect Dis 2012 Nov 1555101320-1328
CSP403C the Long-Term Persistence Substudy was initiated in March 2006 and enrolled 6867 vaccine recipients from the main efficacy study Enrollment was restricted to vaccine recipients from the main efficacy study with no history of herpes zoster This study was initiated to complete an additional five-years of follow-up post-vaccination The objective of this study was to estimate the longer-term durability of zoster vaccine efficacy by following a cohort of vaccine recipients from the primary efficacy study for three study outcomes 1 the incidence of herpes zoster 2 the incidence of postherpetic neuralgia PHN and 3 the burden of illness BOI due to herpes zoster The study completed surveillance for new cases of herpes zoster as of December 2010 and completed the follow-up of the last case of herpes zoster in February 2011 All study sites have been closed out This substudy has been completed and is in the final analysis phase
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None