Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202003634132762 Date of Approval: 18/03/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Use of Gardasil to prevent Cervical Cancer in patients with HIV infection taking antiretroviral drugs
Official scientific title A Randomized, Placebo-Controlled Trial of HPV Vaccination to Reduce Cervical High-Grade Squamous Intraepithelial Lesions among HIV-Infected Women Participating in an HPV Test-and-Treat Program (COVENANT) A Trial of the AIDS Malignancy Consortium (AMC)
Brief summary describing the background and objectives of the trial Cervical cancer is a common problem in Sub-saharan Africa. It is preventable by vaccination, however it is not clear whether sexually experienced, HIV-positive women can benefit. This trial aims to answer this question. HIV-infected females 25 and older, currently receiving antiretroviral therapy for at least 6 months with no prior history of cervical, vulvar, or vaginal cancer. Participants must be HPVpositive by GeneXpert hrHPV assay with HPV16, 18/45, or 31/33/35/52/58 detected. Participants must not have had a hysterectomy, prior treatment for cervical HSIL or prior HPV vaccination. The Main objective is To determine if HPV vaccination reduces the occurrence of cervical HSIL among HIV-infected women participating in an HPV test-and-treat strategy for cervical cancer prevention. Other objectives are:To describe occurrence of cervical HSIL from week 52 to week 104. • To examine the predictors of sustained absence of cervical HSIL through week 104 and clearance of HPV infections after cervical treatment, including: baseline types and quantity of HPV, presence of HSIL at baseline, cryotherapy vs. LEEP, CD4+ cell count, plasma HIV-1 RNA, ART use, age, sexual behavior, and vaccination use. • To compare, between study arms, incident cervical vaccine type HPV infections and cervical cytology results. • To describe prevalent and incident vulvar HSIL or cancer in this population.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) COVENANT
Disease(s) or condition(s) being studied Cancer
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Prevention: Vaccines
Anticipated trial start date 27/04/2020
Actual trial start date 27/04/2020
Anticipated date of last follow up 30/04/2024
Actual Last follow-up date 29/04/2024
Anticipated target sample size (number of participants) 536
Actual target sample size (number of participants) 536
Recruitment status Not yet recruiting
Publication URL https://www.cancer.gov/about-nci/organization/oham/hiv-aids-research/oham-research/aids-malignancy-consortium
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Simple randomization using a randomization table created by a computer software program Central randomisation by phone/fax Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Vaccine 0.5ML at week 1, week 4,and week 26 one dose per week. One vial of 9vHPV will be used.. Prior to injection, the pharmacist or designee will shake the vaccine vial well before use. Thorough agitation immediately before administration is necessary to maintain suspension of the vaccine.After thorough agitation, 9vHPV vaccine will be a white, cloudy liquid. Do not use the product if particulates are present or if it appears discolored. 268
Control Group Sodium chloride 0.5ml At week 1, week 4, and week 26 Sodium chloride will be injected as placebo 268 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. HIV-1 infection, documented by one of the following any time prior to study entry: • Any licensed rapid HIV test. • HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit. And confirmed by one of the following: • Licensed western blot. • Second antibody test by a method other than the initial rapid HIV and/or E/CIA. • HIV-1 antigen. • Plasma HIV-1 RNA viral load. • Documentation of receipt of antiretroviral therapy. 2. HPV positive by the GeneXpert hrHPV assay with HPV16, HPV 18/45, or HPV31/33/35/52/58 detected. 3.Age ≥ 25 years. 4. Receipt of ART for at least 180 days prior to randomization. 5. Participants of childbearing potential, defined as a sexually mature woman who: (1) has not undergone a hysterectomy or bilateral oophorectomy or (2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months), must have a negative urine or serum pregnancy test within 3 weeks prior to enrollment and agree to use an effective form of contraception (e.g., barrier contraception or hormonalcontraception), delaying pregnancy for at least 12 months and ideally for the duration of the study 6. If the participant is of childbearing potential, she should be at least 3 months postpartum. 7. Karnofsky score >70% 8.Ability to understand and the willingness to sign a written informed consent document. 1. Current STI requiring treatment (women may participate after adequate treatment, at the discretion of the treating provider). 2. History of allergic reactions attributed to compounds of similar chemical or biologic composition to Gardasil or Gardasil 9. 3. Uncontrolled intercurrent illness that would limit compliance with study requirements. 4. Prior hysterectomy with removal of the cervix. 5. Prior treatment for cervical HSIL. 6. Prior history of cervical, vulvar, or vaginal cancer. 7. Cervical, vulvar, or vaginal lesions suspicious for cancer based on clinical appearance (e.g. necrotic, ulcerated, and/or fungating masses), unless biopsies show no invasive cancer. 8. Known bleeding diathesis. 9. Prior HPV vaccination. 10. Current or planned use of anticoagulants other than aspirin or non-steroidal antiinflammatory agents. 11. Documentation of WHO Clinical Stage 3 or 4 condition within 6 months of entry. 12. CD4 count <200 cells/mm3 within 6 months of entry. Adult: 19 Year-44 Year,Middle Aged: 45 Year(s)-64 Year(s) 25 Year(s) 65 Year(s) Female
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 08/09/2017 Institutional Research and Ethics Committe
Ethics Committee Address
Street address City Postal code Country
Nandi road Eldoret 30100 Kenya
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 08/09/2019 Institutional Research and Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Nandi Road Eldoret 30100 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Cervical HSIL or invasive cervical cancer diagnosed after the week 4 visit through week 52 post-randomization. week 4, 26, 52, 78, and week 104
Primary Outcome Primary endpoint Cervical HSIL or invasive cervical cancer diagnosed after the week 4 visit through week 52 post-randomization. WEEK 4, 26, 52,78,104
Secondary Outcome Secondary endpoints To describe occurrence of cervical HSIL from week 52 to week 104 • Cervical HSIL diagnosed after the week 52 visit through week 104 postrandomization To examine the predictors of sustained absence of cervical HSIL through week 104 and clearance of HPV infections after cervical treatment, including: baseline types and quantity of HPV, presence of HSIL at baseline, cryotherapy vs. LEEP, CD4+ cell count, plasma HIV-1 RNA, ART use, age, sexual behavior, and vaccination use • Cervical HSIL diagnosed after the week 4 visit through week 104, HPV DNA PCR, hrHPV testing by Xpert To compare, between study arms, incident cervical vaccine type HPV infections and cervical cytology results. • HPV DNA PCR, cervical cytology WEEK 4, 26,52,78.104
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Moi University School of Medicine Nandi Road Eldoret 30100 Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
National Cancer Institute Office of HIV and AIDS Malignancy 31 Center Drive, ROOM 3A33 Bethesda MD 208522440 United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Secondary Sponsor AIDS Malignancy Consortium 401 North Washington Rockville MD 20850 United States of America Other Collaborative Groups
COLLABORATORS
Name Street address City Postal code Country
Carla Chibwesha 103 S Chapel Hill 27599 United States of America
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Elkanah Omenge bworango2000@yahoo.com +254722609132 Nandi Road
City Postal code Country Position/Affiliation
Eldoret 30100 Kenya Gyneoncologist and Senior Lecturer
Role Name Email Phone Street address
Public Enquiries Job Kisuya jobiwapash@yahoo.com +254721884347 Nandi Road
City Postal code Country Position/Affiliation
Eldoret 30100 Kenya Immunologist
Role Name Email Phone Street address
Scientific Enquiries Naftali Busakhala nbusakhala@yahoo.com +254722496933 Nandi
City Postal code Country Position/Affiliation
Eldoret 30100 Kenya Physician and Senior Lecturer
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes We will avail cleaned data to journals and any other appropriate people interested in manuscripts coming out of this study. Study Protocol 1-2 weeks of requesting Formal application
URL Results Available Results Summary Result Posting Date First Journal Publication Date
http://pub.emmes.com/study/amc/public/CurrentStudies/CurrentStudies.htm No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information