Performance, Safety, and Efficacy of a New Cryotherapy Device for Cervical Dysplasia [Part II] (CryoPop)

January 12, 2022 updated by: Jhpiego

Performance, Safety, and Efficacy of a New Cryotherapy Device for Cervical Dysplasia

Globally, cervical cancer is the second most common cancer for women and kills approximately 250,000 women every year, with the annual number of deaths expected to increase to 410,000 by 2030. The majority (88%) of these deaths occur in low- and middle-income countries (LMICs) where screening and prevention services are limited. Prevention of cervical cancer by identification and treatment of cervical cancer precursors is key, since treatment resources for invasive disease are scarce. A cervical cancer screening program cannot be effective unless it is linked with a proven intervention to prevent the development of cervical cancer. The World Health Organization (WHO) recently released the WHO guidelines for screening and treatment of precancerous lesions for cervical cancer prevention, which recommends a screen-and-treat approach for cervical cancer prevention, with cryotherapy being the first choice of treatment for women who have a positive screen. However, these programs are still slow to be implemented in part due to the current high cost and low efficiency of cryotherapy equipment that is often prone to breaking. Jhpiego, an affiliate of Johns Hopkins University (JHU), has developed a new cryotherapy device, CryoPop, that is one tenth the cost of current equipment while also ten times more efficient. Once proven safe, feasible and effective, CryoPop could save tens of thousands of lives in low- and middle-income countries each year by preventing cervical cancer.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The World Health Organization (WHO) Guidelines for screening and treatment of precancerous lesions for cervical cancer prevention recommends a screen- and-treat approach for cervical cancer prevention, with cryotherapy being the first choice of treatment for women who have a positive screen. Cryotherapy using nitrous oxide (N2O) or carbon dioxide (CO2) to induce cryonecrosis of dysplastic tissues followed by regeneration of normal cervical epithelium is the most common intervention used in LMICs because it is simple and safe enough for competently-trained mid-level providers such as nurses and midwives to operate, and can be performed without anesthesia or electricity. Adverse effects after cryotherapy are relatively uncommon and generally minor, reported in 1-2% of women. A recent meta-analysis of 77 studies (with moderate to high quality evidence) regarding the effectiveness of cryotherapy found cure rates of 92% and 85%, respectively, in CIN 2 and CIN 3. Cure was defined as normal cytology or disease-free state (generally with colposcopy +/- biopsy) at the follow-up visit, implying absence of persistent disease or recurrent lesions after treatment and length of follow-up varied from 3 months to 10 years. A more recent systematic review and meta-analyses of benefits and harms of cryotherapy, as well as Loop Electrosurgical Excision Procedure (LEEP) and cervical conization (167 studies) found a residual/ recurrence rate of cervical dysplasia (CIN 2-3) of 5% at 12 months' follow-up. Major and minor adverse events occurred in less than 1% of women and were fewer with cryotherapy than with the other approaches. Limited data suggests that preterm delivery in subsequent pregnancy may be increased (<2%) with cryotherapy or LEEP.

Cost, reliability, durability, portability and reparability are all factors that prohibit the scale-up necessary for current cryotherapy methods to match the volume of population-based screening needed to achieve a marked decrease in cervical cancer morbidity and mortality. Each cryotherapy unit costs approximately $2,000-$7500, resulting in approximately 80% or more of the treatment cost of cryotherapy being directly attributed to equipment cost. The design involves many custom parts available only through the manufacturers, which are all based in the US or Europe. This prohibits local repairs and limits the life of the product to only one or two years (or even less when spare parts are not available). Additionally, the current technology requires huge amount of N20 or CO2 requiring large gas cylinders which are heavy and costly-the cost to refill a CO2 tank can be up to $200.

The subject of this proposal, CryoPop, is a new technology specifically designed for LMIC settings and more appropriate to support see-and-treat efforts because of its low cost, portability, reparability and durability. The CryoPop device is currently expected to cost one half of the price of current devices while also using one tenth of the CO2 supply, thereby substantially reducing the recurring cost of refilling a smaller and more portable gas supply with far greater efficiency in the use of CO2. Moreover, this device is designed to have minimal moving components which at the same time are inexpensive to replace and easy to repair in- situ by the providers themselves. Finally, the CryoPop is not tethered to the gas canister during the procedure, adding more safety to the treatment procedure by not having to be concerned over tank or gas line placement.The goal is to have a device for the frontline where screening is happening and provide the unique opportunity of minimizing if not preventing loss to follow-up of screen-positive women.

This will accelerate access to cervical cancer prevention and treatment services by enabling implementation of single-visit approach (SVA) to rural, underdeveloped regions, most of which have never had cervical cancer prevention (CECAP) programs.

This clinical trial is Part 2 of a 2-part research study. Part 1 of this research study is registered under:

1UH2CA189923-01 Performance, Safety, and Efficacy of a New Cryotherapy Device for Cervical Dysplasia NCT02367625

Study Type

Interventional

Enrollment (Actual)

15

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • India
    • Karnataka
      • Belgaum, Karnataka, India, 590010
        • JN Medical College

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

30 years to 49 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  1. Must be 30-49 years old
  2. High-grade squamous intraepithelial lesion of the cervix (CIN 2/3), confirmed on histology
  3. Eligible for cryotherapy based on size of lesion (occupies <75% of cervix) and fully visible on colposcopy or visual inspection with acetic acid (VIA)
  4. Willing and able to provide consent.

Exclusion Criteria:

  1. Menopausal
  2. History of hysterectomy
  3. Known HIV+ or active cervical infections
  4. Lesion occupies >75% of cervix and/or extends into the endo cervical canal
  5. Pregnancy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Cervical Cytology
100 women with abnormal cervical cytology will receive cryotherapy with the experimental CryoPop device
Device: CryoPop
The new CryoPop device will be tested on women with abnormal cytology. Benchmark testing occurred in the previous study and CryoPop was found to be non-inferior to standard cryotherapy device (MedGyn) in woman with normal cytology.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy of CryoPop: negative Pap smear and negative biopsy (if performed) on each study participant.
Time Frame: 6 months
The proportion of pap smears and colposcopy/biopsies that are negative (have no dysplasia or cancer) as confirmed by Pap smear and/or biopsy read by 2 or 3 pathologists. If there is discordance between the Pap and biopsy readings, the reading with the greater abnormality will have priority as an endpoint.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety of CryoPop: Incidences of adverse events documented throughout the study.
Time Frame: 6 months
Percent of adverse events (AE) and serious adverse events (SAE) will be reported for the study sample. These values will be compared to the safety profile reported for another standard commercially available cryotherapy device.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jhpiego

Collaborators

Jawaharlal Nehru Medical College

Investigators

  • Principal Investigator: Jean Anderson, MD, janders@jhmi.edu

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

April 9, 2019

Primary Completion (ACTUAL)

October 31, 2021

Study Completion (ACTUAL)

November 30, 2021

Study Registration Dates

First Submitted

October 29, 2019

First Submitted That Met QC Criteria

November 5, 2019

First Posted (ACTUAL)

November 6, 2019

Study Record Updates

Last Update Posted (ACTUAL)

January 14, 2022

Last Update Submitted That Met QC Criteria

January 12, 2022

Last Verified

January 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1UH3CA189923-01 (NIH)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data and research materials will be made available for public access upon the completion of the data collection. This data will be shared through the JHU Data Archive, which uses an established repository platform (Dataverse) and is supported by preservation practices, with administrative help for preparing deposits provided by Johns Hopkins Data Services. Deposited data is given standard data citations and persistent identifiers (DOIs) and will be archived for a minimum of 5 years, with the possibility of renewal.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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