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

Brief Title

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

Official Title

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

Brief Summary

      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.
    

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

Primary Outcome

Efficacy of CryoPop: negative Pap smear and negative biopsy (if performed) on each study participant.

Secondary Outcome

 Safety of CryoPop: Incidences of adverse events documented throughout the study.

Condition

Cervical Dysplasia

Intervention

CryoPop

Study Arms / Comparison Groups

 Cervical Cytology

Description:  100 women with abnormal cervical cytology will receive cryotherapy with the experimental CryoPop device

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Device

Estimated Enrollment

15

Start Date

April 9, 2019

Completion Date

November 30, 2021

Primary Completion Date

October 31, 2021

Eligibility Criteria

        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
      

Gender

Female

Ages

30 Years - 49 Years

Accepts Healthy Volunteers

No

Contacts

Jean Anderson, MD, , 

Location Countries

India

Location Countries

India

NCT ID

NCT04154644

Organization ID

1UH3CA189923-01

Responsible Party

Sponsor

Study Sponsor

Jhpiego

Collaborators

 Jawaharlal Nehru Medical College

Study Sponsor

Jean Anderson, MD, Principal Investigator, [email protected]

Verification Date

January 2022