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CTRI Number  CTRI/2013/11/004140 [Registered on: 13/11/2013] Trial Registered Retrospectively
Last Modified On: 30/08/2014
Post Graduate Thesis  Yes 
Type of Trial  PMS 
Type of Study   Vaccine
Preventive 
Study Design  Randomized, Parallel Group Trial 
Public Title of Study   To assess potential hazards, including immediate adverse events after bivalent and quadrivalent HPV vaccines immunizations in healthy Indian women aged 18-25 years. 
Scientific Title of Study   Comparison of Post-licensure safety surveillance of Bivalent and Quadrivalent Human Papillomavirus vaccines in Healthy Women.  
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Vikrant Chandrakant Sangar  
Designation  PhD. Student 
Affiliation  B. J. Govt. Medical College, Pune 
Address  B. J. Govt. Medical College, Near Pune Railway Station, Pune, MAHARASHTRA, India.

Pune
MAHARASHTRA
411001
India 
Phone  9623265391  
Fax    
Email  vikrant_sangar2010@yahoo.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr B B Ghongane 
Designation  Head of Department of Pharmacology 
Affiliation  B. J. Govt. Medical College, Pune 
Address  B. J. Govt. Medical College, Near Pune Railway Station, Pune, MAHARASHTRA, India.

Pune
MAHARASHTRA
411001
India 
Phone  9922925590  
Fax    
Email  ghongane.phdguide@gmail.com  
 
Details of Contact Person
Public Query
 
Name  Vikrant Chandrakant Sangar  
Designation  PhD. Student 
Affiliation  B. J. Govt. Medical College, Pune 
Address  B. J. Govt. Medical College, Near Pune Railway Station, Pune, MAHARASHTRA, India.

Pune
MAHARASHTRA
411001
India 
Phone  9623265391  
Fax    
Email  vikrant_sangar2010@yahoo.com  
 
Source of Monetary or Material Support  
Madhusudan B. Vakharia. 1601, Veena Towers, Opposite Colaba Post Office, Colaba, Mumbai-400005. Money funded for purchasing HPV vaccines. 
 
Primary Sponsor  
Name  Madhusudan B Vakharia 
Address  1601, Veena Towers, Oppo. Colaba POst Office, Colaba, Mumbai-400005. 
Type of Sponsor  Other [Businessman] 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 1  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr B B Ghongane   B. J. Govt. Medical college and Sassoon General Hospitals, Pune  B. J. Govt. Medical College and Sassoon General Hospitals, Pharmacology Department, 2nd Floor, Near Pune Railway Station, Pune-1
Pune
MAHARASHTRA 
9922925590

ghongane.phdguide@gmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 2  
Name of Committee  Approval Status 
BJGMC/IEC/Pharma/NC-Dept 0312017-17  Approved 
HITRTparel  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Healthy Human Volunteers  To prevent cervical cancer 
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  GSK Biologicals HPV vaccine  Subjects will receive three doses of the study vaccine administered intramuscularly according to a Day 0, 1 and Month 6 vaccination schedule 
Intervention  Merck s Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine  Subjects will receive three doses of the study vaccine administered intramuscularly according to a Day 0, 2 and Month 6 vaccination schedule. 
Comparator Agent  Nil  Nil 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  25.00 Year(s)
Gender  Female 
Details  1. Able to fill the questionnaires used in this study.
2. Able to give a written informed consent.
3. Able to attend all scheduled visits. 
 
ExclusionCriteria 
Details  1. No hospitalization within 21 days prior to study entry.
2. Oral temperature of 38.3 C (101 F) or greater within 72 hours prior to each study vaccination.
3. Hypersensitivity to latex.
4. Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
5. They have surgery planned during the study period.
6. Pregnant or immune compromised women should be avoided.
7. Any other condition including abuse of alcohol, drug addiction of imposed confinement that may interfere with ability to comply with trial procedures.  
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Centralized 
Blinding/Masking   Participant and Outcome Assessor Blinded 
Primary Outcome  
Outcome  TimePoints 
1. To evaluate potential local injection site reactions and serious adverse events within 7 and 30 days after each dose of prophylactic bivalent and quadrivalent HPV vaccine.   1 year 
 
Secondary Outcome  
Outcome  TimePoints 
1. To determine the occurrence, nature, duration, severity and relationship to vaccination of any local injection site reactions and serious adverse events.

2. To monitor whether the adverse events reported after vaccination with prophylactic bivalent and quadrivalent HPV vaccines the same as those expected and listed in the package insert.  
12 months 
 
Target Sample Size   Total Sample Size="70"
Sample Size from India="70" 
Final Enrollment numbers achieved (Total)= ""
Final Enrollment numbers achieved (India)="" 
Phase of Trial   Post Marketing Surveillance 
Date of First Enrollment (India)   01/03/2013 
Date of Study Completion (India) Date Missing 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Date Missing 
Estimated Duration of Trial   Years="1"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Not Applicable 
Recruitment Status of Trial (India)  Completed 
Publication Details   Not yet 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Brief Summary  

Cervical cancer (CaCx) is one of the leading causes of morbidity and mortality among the gynecological cancer worldwide. Each year approximately 529,409 women are diagnosed with cervical cancer. In 2008, mortality is staggering at 274,883 lives lost each year. About 86% of the cases occur in developing countries and may constitute up to 25% of all female cancers.

In India this cervical cancer is reported to be responsible for almost 20 percent of all female deaths and takes the lives of 8 women in India every hour. India with a population of 365.71 million has women aged between 15 years and above who stand at the risk of developing cervical cancer. India recorded 134420 new cases out of these cases 72825 cases lost their lives. Cervical cancer age-standardized incidence rate of 30.7 per 100,000 is more than 300% higher than rates in the United States and other countries including United Kingdom and Canada. Cervical cancer mortality at 18.6 per 100,000 is more than 8 times higher than the United States and almost 11 times higher than Australia.

Numerous clinical evidences have established the human papillomavirus (HPV) as a necessary cause of cervical cancer. Knowledge of this association has spurred research on HPV based strategies for cervical cancer prevention, including primary prevention of HPV, HPV vaccines, and the use of HPV testing. At the same time it is crucial to conduct post marketing surveillance in order to decide whether it is important to implement this HPV vaccine for public health and whether the adverse events reported after vaccination with prophylactic bivalent and quadrivalent HPV vaccines the same as those expected and listed in the package insert


AIMS AND OBJECTIVES: -

This study is carried out among medical personnel to assess-

1. To evaluate potential local injection site reactions and serious adverse events within 7 and 30 days after each dose of prophylactic bivalent and quadrivalent HPV vaccine.

 

2. To determine the occurrence, nature, duration, severity and relationship to vaccination of any local injection site reactions and serious adverse events.

 

3. To monitor whether the adverse events reported after vaccination with prophylactic bivalent and quadrivalent HPV vaccines the same as those expected and listed in the package insert.

 

MATERIAL & METHODS: -

Study Design:

This is observational cohort study of participants who are immunized with prophylactic bivalent and quadrivalent HPV vaccine and followed actively for safety outcomes during 7 and 30 days after each dose of prophylactic bivalent and quadrivalent HPV vaccine. In order to achieve the study objectives, the protocol will be carried out in several settings using the same design. The invitation to participate and conduct these studies will be extended to health departments and healthcare facilities that routinely conduct HPV vaccine immunization. 

 

Written consent from eligible women will be obtained. Participants will be made to read an information sheet about the project and the project will be explained to them in the language they understand. The investigator will provide a copy of the signed informed consent to the subject, and will maintain the original in the investigator’s study file. A person who is qualified according to applicable local regulations will conduct the informed consent discussion. The subject should be given the opportunity to inquire about details of the study and to consider participation. These women will be asked few questions related to cervical cancer and HPV vaccines and answers will be noted. Reproductive tract infections related history would be taken from participants. Strict privacy and confidentiality will be maintained during interview and in the entire phase of the study. The subject should be informed in a timely manner if new information becomes available that might affect the decision to participate in the study. The communication of this information should be documented.

 

Prior to immunization any injection site clinical findings that could impact on the assessment of local l injection site reactions will be documented (such as existing rash, bruising and so on). While in the immunization clinic, subjects will be shown how to complete all subject report forms and taught the correct method for taking an oral temperature daily using a digital thermometer and for using the plastic template (containing 5 circles of increasing diameter from 1 to 5 cm) to measure the size of any injection side redness, swelling, induration or bruising. In addition, subjects will be instructed to repeat the temperature measurement any time they feel feverish and to record the value and time taken on the diary card.

Subjects will be kept under observation for a time period in accordance with local standard of practice. It is preferable that subjects be reexamined 30 minutes after immunization for any local or systemic reactions. In health care situations where employees would normally return to work before the 30 minute time point, phone follow-up to record the 30 minute observations is acceptable but arrangements should be made to examine any who report moderate to severe local or systemic reactions. Other observations to be recorded in the diary card each day for the 7 days following immunization include-

·         daily assessment of the presence or absence, and if the former, the maximal

severity of pain at the injection site, headache, feeling unwell, aches/pains or chills/ shivering. Levels of severity are defined as:

mild- present but doesn’t interfere with daily activities

moderate- interferes with daily activities

severe- unable to do daily activities

  • daily measurement of the maximum diameter of any redness, swelling,

inducrtion or bruising at the injection site(<1cm; 1to<2cm; 2to<3 cm; 3to<4 cm; 4to<5 cm; ≥5 cm).  For these purpose templates with 5 circles of diameters 1, 2, 3, 4 and 5 cm will be provided.   

 

Reactogenicity

Subjects will use a separate diary cards to record the occurrence of unsolicited signs after each vaccine dose. SAEs, MSCs (defined as AEs prompting emergency room or physician visits that wil not related to common diseases or SAEs that will not related to common diseases), pregnancy outcomes and withdrawals due to AEs/SAEs will be reported throughout the entire study period. Examples of common diseases not included in the definition of MSC will be upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervicovaginal yeast infections, menstrual cycle abnormalities and injury. Decisions relating adverse events to vaccination will be based on the judgment of the investigator at the study site reporting the event.

 

All data are to be captured using the paper case report form. Any AE/SAE will be documented to respective vaccine adverse event reporting system.

 

SELECTION OF CASES: -  

Inclusion/Exclusion Criteria

1.      Inclusion:

Subjects eligible for enrolment into this study are healthy female adult volunteers who are:

  1. able to attend all scheduled visits
  2. able to give written informed consent prior to study entry.

 

2.      Exclusion:

Individuals are not to be enrolled into the study if:

       1. No hospitalization within 21 days prior to study entry.

       2. Oral temperature of 38.3 C (101 F) or greater within 72 hours prior to each study vaccination.

       3. Hypersensitivity to latex.

       4. Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.

       5. They have surgery planned during the study period

       6. Pregnant or immune compromised women should be avoided.

       7. Any other condition including abuse of alcohol, drug addiction of imposed confinement that may interfere with ability to comply with trial procedures 

 

ADVERSE EVENTS/ RISKS/ ETHICAL CONSIDERATIONS: -  

Risks to confidentiality will be minimized by de-identifying patient information and assigning a unique number to each patient. This data would be stored on a password-protected computer and be accessible only to the study personnel. All patient data including consent forms will be kept in a locked filing cabinet accessible only to the project personnel. To assure confidentiality, all the survey results will be recorded by study ID number only and will not be recorded directly in the study participant’s chart, to avoid inadvertent release of confidential information. All computer entry and networking programs will be done with coded numbers only. Electronic data will be kept in a password-protected computer with access provided only to the study personnel.

 

 
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