The HPV 9-10 Trial: Early Initiation of HPV Vaccination

• ClinicalTrials.gov Identifier: NCT04722822
• Recruitment Status: Recruiting
• First Posted: January 25, 2021
• Last Update Posted: June 30, 2022
• Sponsor: University of Colorado, Denver
• Collaborators: National Institutes of Health (NIH); National Cancer Institute (NCI)
• Information provided by (Responsible Party): University of Colorado, Denver

Study Description

Brief Summary:

Every year, thousands of Americans die from cancers related to human papillomavirus (HPV). The vast majority of those deaths could be prevented with a safe and effective vaccine, yet many parents choose not have their children vaccinated when it is recommended at age 11 or 12. In this study, we will examine in a randomized trial whether earlier initiation of the vaccine at age 9-10 years will result in less parental refusal and higher rates of full vaccination at younger ages, before early sexual activity begins.

Condition or disease	Intervention/treatment	Phase
HPV	Behavioral: (Intervention) Recommending HPV vaccine for patients 9-10 years of age; Behavioral: (Control) Recommending HPV vaccine for patients 11-12 years of age	Not Applicable

Detailed Description:

The burden of Human Papillomavirus (HPV)-related disease in the US is substantial. A safe and effective vaccine has been available for >10 years, yet the current rate of completion for the HPV series is only 49% for U.S.13-17 year olds. The Advisory Committee on Immunization Practices (ACIP) recommends routine HPV vaccination at age 11-12 years (yrs), but states that the vaccine "can be given starting at age 9 years." Currently, the majority of pediatricians begin recommending the vaccine at ages 11-12 yrs, however, a recent retrospective study showed that on-time completion rates for HPV vaccine were much higher when the vaccine series was initiated at ages 9-10 compared to ages 11-12 (adjusted odds ratio, 12.8).

HPV vaccine should be given prior to sexual activity which occurs earlier than 13 yrs for many teens. There are compelling reasons to think that earlier initiation of vaccination at ages 9-10 might result in higher rates of acceptance of the vaccine and earlier series completion. First, many parents refuse HPV vaccine because they have concerns that vaccination could result in higher promiscuity in early adolescents if the vaccine is discussed in the context of sexuality. Initiation at 9-10 yrs, when few providers discuss sex, could put the focus squarely on cancer prevention, decreasing vaccine refusal. Second, three vaccines are recommended at the 11-12 yr visit, but many parents/adolescents are unwilling to receive all three at one visit. When one of the vaccines is delayed, it is almost always HPV vaccine. Initiation at 9-10 yrs when no other vaccines are given could result in less deferral of vaccination to mid-adolescence and higher rates of vaccination prior to early sexual activity. Finally, initiation at age 9-10 years has been shown to be feasible and, in an observational study, to result in higher rates of on-time series completion.

Therefore, we plan to test the effectiveness of shifting initiation of HPV vaccine to 9-10 yrs in a randomized pragmatic trial. Our Specific Aims are to: SA 1: Recruit practices in two states (Colorado and California), randomize in a balanced fashion to recommending HPV vaccine at ages 9-10 yrs or 11-12 yrs and provide standardized training to both arms. SA 2: Conduct a trial to assess effectiveness of early initiation on the primary outcome of age at HPV series completion; secondary outcomes will examine HPV series completion by age 13 and age at HPV series initiation. SA 3: Examine the effect of earlier initiation on length of time for HPV vaccine discussions and on parent/provider communication about HPV vaccine via audio-taping of visits, audio-elicitation interviews with parents and structured interviews with providers and clinic staff.

If earlier HPV initiation is successful in promoting higher HPV series completion by 13 yrs, this intervention could be rapidly disseminated and would have the potential to prevent thousands of cases of HPV-related cancers, their attendant morbidity and mortality as well as the costs of screening, diagnosis and treatment for these cancers yearly.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 660 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Masking Description: Investigator and data analysis team will be blinded to the arms during analysis. Practices (unit of randomization) cannot be blinded; however patients who are subjects of the intervention are not aware of the group allocation of the practice in the clinical trial.
• Primary Purpose: Health Services Research
• Official Title: The HPV 9-10 Trial: Early Initiation of HPV Vaccination
• Actual Study Start Date: December 23, 2019
• Estimated Primary Completion Date: April 2025
• Estimated Study Completion Date: April 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Providers recommending HPV vaccine at age 9-10 years of age; Providers in this arm will routinely recommend HPV vaccine starting at 9-10 years of age.	Behavioral: (Intervention) Recommending HPV vaccine for patients 9-10 years of age; Providers within intervention practices will receive training which includes both standardized communication strategies and strategies for switching from 11-12 years to 9-10 years including: challenges with 11-12 strategy, long-term immunity, success of other practices and tips to help standardize to age 9-10. Trainings will be a combination of online and in-person or virtual. Annual trainings will be offered and providers will receive Maintenance of Certification credits (MOC) for participating. Providers will routinely recommend HPV starting at age 9 for all patients -- which is already approved for this vaccine but is not routinely recommended at age 9 years.
Active Comparator: Providers recommending HPV vaccine at age 11-12 years of age; Providers in this arm will routinely recommend HPV vaccine starting at 11-12 years of age.	Behavioral: (Control) Recommending HPV vaccine for patients 11-12 years of age; Providers within control practices will receive a training on standardized communication for HPV vaccine including: using strong recommendations, using presumptive recommendation, providing specific phrases to use with parents, answering common questions and, HPV vaccine as a cancer prevention. Annual trainings will be offered and providers will receive professional development credit (MOC).

Outcome Measures

Primary Outcome Measures :

1. Age at completion of two dose HPV series [ Time Frame: post-intervention assessed in year 5 of study, year 4 of trial ]
   The primary outcome will be age at completion of the two dose HPV series. This is a time-to-event outcome, with the event of interest being vaccine completion. Comparisons between the intervention practices and control practices will be made. Practice electronic health records will be used to assess this outcome.

Secondary Outcome Measures :

1. HPV completion by age 13 years [ Time Frame: post-intervention assessed in year 5 of study, year 4 of trial ]
   Secondary outcome will be HPV series completion rates by age 13. This will be a binary outcome. Comparisons between the intervention practices and control practices will be made. Practice electronic health records will be used to assess this outcome.
2. Age at initiation of the HPV series [ Time Frame: post-intervention assessed in year 5 of study, year 4 of trial ]
   This is a time-to-event outcome, with the event of interest being vaccine initiation. Comparisons between the intervention practices and control practices will be made. Practice electronic health records will be used to assess this outcome.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Practices:

Inclusion Criteria:

• Practices in Metro Denver, Colorado and Metro Los Angeles, California (specifically UCLA medical clinics and clinics affiliated with Children's Hospital of Orange County)
• Practices that have at least 60% of providers agree to participate
• Practices do not currently recommend HPV at 9-10 years.
• Practice must have at least 100 eligible patients age 9-13 years

Exclusion Criteria:

• Practices with less than 100 eligible patients age 9-13 years
• Practices currently routinely recommend HPV vaccine at 9-10 years.
• Practices where less than 60% of providers agree to participate in the study.

Patients whose data will be used to assess the outcomes of the intervention will be age 9-13 years old.

Contacts and Locations

Contacts

Contact: Alison Saville, MPH, MSW; 720-257-4406; alison.saville@cuanschutz.edu

Locations

United States, California

University of California at Los Angeles; Not yet recruiting

Los Angeles, California, United States, 90095

Contact: Abigail Breck abreck@mednet.ucla.edu

Principal Investigator: Peter Szilagyi, MD, MPH

United States, Colorado

University of Colorado; Recruiting

Aurora, Colorado, United States, 80045

Contact: ALISON W SAVILLE, MPH, MSW 720-257-4406 alison.saville@cuanschutz.edu

Principal Investigator: Allison Kempe, MD, MPH

Sponsors and Collaborators

University of Colorado, Denver

National Institutes of Health (NIH)

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Allison Kempe, MD, MPH; University of Colorado, Denver

More Information

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT04722822
• Other Study ID Numbers: 19-3006.cc; 1R01CA240649-01A1 ( U.S. NIH Grant/Contract )
• First Posted: January 25, 2021
• Last Update Posted: June 30, 2022
• Last Verified: June 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: The study team guarantees that any and all data collected as part of this project will be released in accordance with standard data sharing policies and procedures to validate research findings if requested. Data will be made available in a timely manner to the broader scientific community, and will be complete, and as accurate as possible. All data released will be de-identified, with no information that could be linked to any study subjects, or participating study practices in order to ensure the confidentiality of all subjects and practices. If necessary, a data use agreement will be established.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP)
• Time Frame: May 2025
• Access Criteria: The study team intends to share study data that may be requested from other research investigators in a data-sharing agreement provided at the individual study's end. The data-sharing agreement will include requirements to protect participants' privacy and data confidentiality. It will prohibit the recipient from transferring the data to other users and will require that the data's security be protected by standard means and be used for research purposes only. The method of distribution will be by request to Dr. Kempe (UCAMC) or Dr. Szilagyi (UCLA), the study PIs. After a requestor completes the data-sharing agreement, we will upload data to a secure File Transfer Protocol (FTP) site with the limited dataset to the requestor, or email the data through our University secured email systems that require users to create an account and sign-in with a username and password in order to receive and download any type of sensitive data.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Vaccines; Immunologic Factors; Physiological Effects of Drugs