Cervical Intraepithelial Neoplasia
Conditions
Brief summary
The purpose of this study is to test two innovative devices, the CryoPen® and thermocoagulator, against gas-based cryotherapy to determine whether the novel devices produce equivalent or improved destruction of cervical tissue compared to gas-based cryotherapy. Tissue destruction with single freeze versus double freeze treatments with the CryoPen and gas-based cryotherapy will also be compared.
Detailed description
The primary objectives of the study are to test the hypothesis that the CryoPen® and thermocoagulator provide a non-inferior depth of cervical tissue necrosis compared with traditional CO2-based cryotherapy and to test single versus double freeze applications. The secondary objectives of the study are to determine if the CryoPen® or thermocoagulator achieves a depth of necrosis of 3.5 mm, the accepted depth required for eradicating 95% of cervical precancer, and to observe the relationship between depth of necrosis and variations in cervical anatomy.
Interventions
DEVICECryoPen
Provides a means of freezing tissue without the use of gases or liquids
DEVICECO2 standard cryotherapy
Standard therapy using carbon dioxide for freezing of tissue
DEVICEThermocoagulator
The use of heat produced by high-frequency electric current to bring about local destruction of tissues
Sponsors
National Cancer Institute (NCI)
Basic Health International
CryoPen, Inc.
University of Southern California
Albert Einstein College of Medicine
The Cleveland Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
25 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Between 25 and 65 years old. * Scheduled for a hysterectomy for reasons other than cervical precancer or cancer * Diagnosis of uterine, endometrial, ovarian or other cancer that does not jeopardize the tissue of the cervix is permitted * Histological evaluation of the cervix does not interfere with the woman's current diagnosis * Woman consents to participate after being informed about the study * Normal Pap Smear or HPV test in the past 3 years
Exclusion criteria
* Pregnancy * History of cervical surgery in past 5 years * Presence of cervical lesion pre-invasive or invasive on the cervix \* * Current Pelvic Inflammatory Disorder or severe acute cervicitis * Cervix shape disfigured or hard to reach
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mean Depth of Necrosis Achieved With the LMIC-adapted CryoPen and the Thermocoagulator Compared to Mean Depth of Necrosis Achieved With CO2-based Cryotherapy | 24-48 hours after treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Pain During Treatment Reported by Patients Treated With Double and Single Freeze CO2 Cryotherapy, Double and Single Freeze CryoPen and Thermoablation | 40 seconds to 13 minutes | Scale Title: Pain scale during treatment Minimal value = 0 (no pain) Maximum value = 10 (most pain) This is a one item 11-point scale to measure self-reported pain during each of the treatments which lasted between 40 seconds (thermoablation) and 13 minutes (double freeze cryotherapy and double freeze CryoPen). |
Countries
El Salvador, Peru
Participant flow
Recruitment details
Participants were between the ages of 25 and 65 to be eligible for the study
Participants by arm
| Arm | Count |
|---|---|
| CO2 Standard Cryotherapy- Double Freeze Double freeze treatment consists of three-minute freeze, five-minute thaw, three-minute freeze
CO2 standard cryotherapy: Standard therapy using carbon dioxide for freezing of tissue | 27 |
| CO2 Standard Cryotherapy- Single Freeze Single freeze treatment consists of one five-minute freeze
CO2 standard cryotherapy: Standard therapy using carbon dioxide for freezing of tissue | 24 |
| CryoPen- Double Freeze Double freeze treatment consists of three-minute freeze, five-minute thaw, three-minute freeze
CryoPen: Provides a means of freezing tissue without the use of gases or liquids | 26 |
| CryoPen- Single Freeze Single freeze treatment consists of one five-minute freeze
CryoPen: Provides a means of freezing tissue without the use of gases or liquids | 25 |
| Thermocoagulator Single heat application at 100 ºC for 40 seconds
Thermocoagulator: The use of heat produced by high-frequency electric current to bring about local destruction of tissues | 28 |
| Total | 130 |
Baseline characteristics
| Characteristic | CO2 Standard Cryotherapy- Double Freeze | CO2 Standard Cryotherapy- Single Freeze | CryoPen- Double Freeze | CryoPen- Single Freeze | Thermocoagulator | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants | 24 Participants | 26 Participants | 25 Participants | 28 Participants | 130 Participants |
| Age, Continuous | 45.46 years STANDARD_DEVIATION 6.44 | 45.5 years STANDARD_DEVIATION 6.53 | 45.92 years STANDARD_DEVIATION 5.82 | 44.65 years STANDARD_DEVIATION 5.91 | 45.35 years STANDARD_DEVIATION 6.05 | 45.37 years STANDARD_DEVIATION 5.98 |
| Region of Enrollment El Salvador | 15 Participants | 15 Participants | 16 Participants | 15 Participants | 18 Participants | 79 Participants |
| Region of Enrollment Peru | 12 Participants | 9 Participants | 10 Participants | 10 Participants | 10 Participants | 51 Participants |
| Sex: Female, Male Female | 27 Participants | 24 Participants | 26 Participants | 25 Participants | 28 Participants | 130 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 24 | 0 / 26 | 0 / 25 | 0 / 28 |
| other Total, other adverse events | 0 / 27 | 0 / 24 | 0 / 26 | 0 / 25 | 0 / 28 |
| serious Total, serious adverse events | 0 / 27 | 0 / 24 | 0 / 26 | 0 / 25 | 0 / 28 |
Outcome results
Primary
Mean Depth of Necrosis Achieved With the LMIC-adapted CryoPen and the Thermocoagulator Compared to Mean Depth of Necrosis Achieved With CO2-based Cryotherapy
Time frame: 24-48 hours after treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CO2 Standard Cryotherapy- Double Freeze | Mean Depth of Necrosis Achieved With the LMIC-adapted CryoPen and the Thermocoagulator Compared to Mean Depth of Necrosis Achieved With CO2-based Cryotherapy | 6.0 millimeters | Standard Deviation 1.6 |
| CO2 Standard Cryotherapy- Single Freeze | Mean Depth of Necrosis Achieved With the LMIC-adapted CryoPen and the Thermocoagulator Compared to Mean Depth of Necrosis Achieved With CO2-based Cryotherapy | 5.6 millimeters | Standard Deviation 1.9 |
| CryoPen- Double Freeze | Mean Depth of Necrosis Achieved With the LMIC-adapted CryoPen and the Thermocoagulator Compared to Mean Depth of Necrosis Achieved With CO2-based Cryotherapy | 5.3 millimeters | Standard Deviation 1.2 |
| CryoPen- Single Freeze | Mean Depth of Necrosis Achieved With the LMIC-adapted CryoPen and the Thermocoagulator Compared to Mean Depth of Necrosis Achieved With CO2-based Cryotherapy | 5.5 millimeters | Standard Deviation 1.3 |
| Thermocoagulator | Mean Depth of Necrosis Achieved With the LMIC-adapted CryoPen and the Thermocoagulator Compared to Mean Depth of Necrosis Achieved With CO2-based Cryotherapy | 3.5 millimeters | Standard Deviation 0.9 |
Secondary
Mean Pain During Treatment Reported by Patients Treated With Double and Single Freeze CO2 Cryotherapy, Double and Single Freeze CryoPen and Thermoablation
Scale Title: Pain scale during treatment Minimal value = 0 (no pain) Maximum value = 10 (most pain) This is a one item 11-point scale to measure self-reported pain during each of the treatments which lasted between 40 seconds (thermoablation) and 13 minutes (double freeze cryotherapy and double freeze CryoPen).
Time frame: 40 seconds to 13 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CO2 Standard Cryotherapy- Double Freeze | Mean Pain During Treatment Reported by Patients Treated With Double and Single Freeze CO2 Cryotherapy, Double and Single Freeze CryoPen and Thermoablation | 2.2 units on a scale | Standard Deviation 1 |
| CO2 Standard Cryotherapy- Single Freeze | Mean Pain During Treatment Reported by Patients Treated With Double and Single Freeze CO2 Cryotherapy, Double and Single Freeze CryoPen and Thermoablation | 1.8 units on a scale | Standard Deviation 0.8 |
| CryoPen- Double Freeze | Mean Pain During Treatment Reported by Patients Treated With Double and Single Freeze CO2 Cryotherapy, Double and Single Freeze CryoPen and Thermoablation | 2.5 units on a scale | Standard Deviation 1.4 |
| CryoPen- Single Freeze | Mean Pain During Treatment Reported by Patients Treated With Double and Single Freeze CO2 Cryotherapy, Double and Single Freeze CryoPen and Thermoablation | 2.6 units on a scale | Standard Deviation 1.4 |
| Thermocoagulator | Mean Pain During Treatment Reported by Patients Treated With Double and Single Freeze CO2 Cryotherapy, Double and Single Freeze CryoPen and Thermoablation | 4.1 units on a scale | Standard Deviation 2.3 |