Ignite Creation Date:
2024-05-05 @ 6:52 PM
Last Modification Date:
2024-10-26 @ 9:38 AM
Study NCT ID:
NCT00566579
Status:
TERMINATED
Last Update Posted:
2010-08-10
First Post:
2007-11-30
Brief Title:
Cryotherapy for Human Papillomavirus Clearance in Biopsy-confirmed Cervical Low-grade Squamous Intraepithelial Lesions
Sponsor:
Khon Kaen University
Organization:
Khon Kaen University
Study Overview
Official Title:
Cryotherapy for Human Papillomavirus Clearance in Biopsy-confirmed Cervical Low-grade Squamous Intraepithelial Lesions a Randomized Controlled Trial
Status:
TERMINATED
Status Verified Date:
2007-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Lack of additional funding
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Cryotherapy
Brief Summary:
Persistent human papillomavirus HPV infections is the single necessary cause of cervical cancer Cervical cancer is still the major health problem in the developing countries It has been the first rank womens cancer in Thailand for many decades Approximately 10-20 of Thai women have the high-risk HPV HR-HPV infections in their cervices This will frequently lead to low-grade squamous intraepithelial lesions LSILs 10 high-grade squamous intraepithelial lesions HSILs 08 and finally cervical cancers 016 within 10-20 years The treatment options for LSILs are either observation or ablative surgery However in our institute cryotherapy which is the one of ablative surgery is more frequently used to comfort our women It is not only effective but safe with only minimal side effects watery leukorrhea for 2-4 weeks and local cervical infection not more than 1 Contraindication to this procedure are active cervical infection lesion of 2 mm-larger than probe lesion inside cervical os and suspected cervical cancer Additionally in developing countries such as Thailand this treatment is safe acceptable feasible and effective Patients with LSILs could also have this treatment in some rural area from the 10-days trained nurses Fortunately recent reports showed that cryotherapy has abilities not only in clearing LSILs but also clearing the HPV infections its necessary cause However there are no randomized controlled trial compared its clearing ability between observation and cryotherapy Therefore a randomized controlled trial is needed to demonstrate that Findings from this trial will contribute enormously to older women who already get infected by HPV Aside from preventing cervical cancer in treated woman cryotherapy could also give her relief from worrying about having a time-bomb like HPV infection in her cervix
Detailed Description:
This will be a hospital-based parallel assessor-blinded randomized controlled trial Study subjects refer to LSIL patients more than 30 years-old with positive HPV testing who do not have any contraindication of performing cryotherapy Therefore after recruitment LSIL patients whose age more than 30 years-old we will exclude only those who have negative HPV testing or any contraindications of performing cryotherapy The primary outcome is HPV clearance negative HPV testing for the baseline HPV type at 12 months after the treatment Subjects will be randomly allocated to be treated by cryotherapy or observation only by using block randomization with varied block size of 2 4 and 6 The sample size of at least 25 for each arm was planned to have the power of 80 to detect 20 difference rates of HPV clearance after 12 months of treatment between the two arms with significance level of 005 two-sided test
Study population
Biopsy-confirmed LSIL patients age more than 30 years-old referred to either Srinagarind Hospitals Khon Kaen Hospitals or Roi Et Hospitals colposcopic clinics
Inclusion criteria
Baseline HPV testing is positive
Be able to give their informed consent to this study
Exclusion criteria
Having active cervical infection
Having lesion of 2 mm-larger than probe
Having lesion inside cervical os
Having suspected cervical cancer lesion
Sample and sample size
From previous studies HPV clearance rate after cryotherapy at 12 months is 839 Elfgren 2002 Spontaneous HPV clearance rate in young women at 24 months is 70 Moscicki 1998 However this HPV clearance rate in women older than 34 years-old at 12 months is only 536 Clavel 2005 Using these numbers respectively as PE and PC putting in the formula below we can calculate our sample size in each group The sample size will be calculated to detect the 20-40 difference between the HPV clearance rates after 12 months at significant level of 95 and power of 80 two-sided test using the approach of Lachin that was reviewed in the paper of DonnerDonner 1984
Required sample size at different rate of clearance
P-control P-experimental Alpha level Power N Difference 95CI 050 070 5 80 103 20 69-331 050 075 5 80 66 25 9-41 050 080 5 80 45 30 113-487 050 085 5 80 33 35 14-56 050 090 5 80 25 40 171-629
The sample size of at least 25 patients in each group will be chosen because of its precision and feasibility Such sample size can detect 40 difference of HPV clearance rate between the two groups at 95 significant level with the power of 80 95CI of 171-629 respectively
Instruments
After signing on the consent form all eligible patients will be examined by the baseline standard procedures and PCR-HPV testing for 37 HPV types Only positive HPV testing ones will be enrolled in the trial and then randomized to receive the cryotherapy or observation The method of block randomization with block size varies from 2 to 6 will be used to allocate treatments
The allocation ratio is 11 The allocation sequence will be generated by computer using STATA software version 100
Based on the obtained schedule the number of sealed envelopes which are equal to the required blocks will be prepared and labeled Each envelope contains the corresponding sealed allocation cards that will allocate treatments to patients
Colposcopy and cryotherapy instruments are available in our colposcopic clinic However we will reimburse for all CO2-gases tanks and materials used for Pap smears and HPV testing
The people who prepare the randomized scheme will not involve in the trial The allocation schedule will be concealed to the assessor who measure the HPV testing until the end of trial
Data collection and measurement
Because of the difference between two treatments only the assessor who measure the HPV testing will be blinded from the treatments
The specimens will be sent to the assessor without patients name or HN that can be linked to the treatment received They will be provided only the study ID number in which only the principle investigator can link it to the treatment received
The main outcome is HPV clearance It is measured by the gold-standard HPV testing This will be performed at baseline and 12 months later
Data analysis
There were two main parts of analysis - describing selected characteristics of the study patients and analysis for answering the research questions The first part selected baseline characteristics of the patients in each treatment were compared ie age sex sexual experiences underlying diseases etc Comparability of the distribution of those selected characteristics based on judgment rather than statistical significant tests In this part proportion was use for summarizing categorical data For continuous data the statistics include mean standard deviation minimum maximum and median
For the second part the analysis was based on the group in which the study patients were randomized intention-to-treat basis The different rate of clearance between the two arms of the trial and its 95 confidence interval will be calculated This will be done at 12 months after the treatment Z-test will be used for testing if such differences are different from zero Multiple logistic regression will be used to control effects of any important confounding factors Absolute risk reduction ARR relative risk reduction RRR and number needed to treat NNT will also be calculated
The statistical analysis of this clinical trial will be performed based on intention-to-treat principle All hypothesis tests are two-tailed at significant level of 005 Statistical package for all analysis is STATA version 100
Study population
Biopsy-confirmed LSIL patients age more than 30 years-old referred to either Srinagarind Hospitals Khon Kaen Hospitals or Roi Et Hospitals colposcopic clinics
Inclusion criteria
Baseline HPV testing is positive
Be able to give their informed consent to this study
Exclusion criteria
Having active cervical infection
Having lesion of 2 mm-larger than probe
Having lesion inside cervical os
Having suspected cervical cancer lesion
Sample and sample size
From previous studies HPV clearance rate after cryotherapy at 12 months is 839 Elfgren 2002 Spontaneous HPV clearance rate in young women at 24 months is 70 Moscicki 1998 However this HPV clearance rate in women older than 34 years-old at 12 months is only 536 Clavel 2005 Using these numbers respectively as PE and PC putting in the formula below we can calculate our sample size in each group The sample size will be calculated to detect the 20-40 difference between the HPV clearance rates after 12 months at significant level of 95 and power of 80 two-sided test using the approach of Lachin that was reviewed in the paper of DonnerDonner 1984
Required sample size at different rate of clearance
P-control P-experimental Alpha level Power N Difference 95CI 050 070 5 80 103 20 69-331 050 075 5 80 66 25 9-41 050 080 5 80 45 30 113-487 050 085 5 80 33 35 14-56 050 090 5 80 25 40 171-629
The sample size of at least 25 patients in each group will be chosen because of its precision and feasibility Such sample size can detect 40 difference of HPV clearance rate between the two groups at 95 significant level with the power of 80 95CI of 171-629 respectively
Instruments
After signing on the consent form all eligible patients will be examined by the baseline standard procedures and PCR-HPV testing for 37 HPV types Only positive HPV testing ones will be enrolled in the trial and then randomized to receive the cryotherapy or observation The method of block randomization with block size varies from 2 to 6 will be used to allocate treatments
The allocation ratio is 11 The allocation sequence will be generated by computer using STATA software version 100
Based on the obtained schedule the number of sealed envelopes which are equal to the required blocks will be prepared and labeled Each envelope contains the corresponding sealed allocation cards that will allocate treatments to patients
Colposcopy and cryotherapy instruments are available in our colposcopic clinic However we will reimburse for all CO2-gases tanks and materials used for Pap smears and HPV testing
The people who prepare the randomized scheme will not involve in the trial The allocation schedule will be concealed to the assessor who measure the HPV testing until the end of trial
Data collection and measurement
Because of the difference between two treatments only the assessor who measure the HPV testing will be blinded from the treatments
The specimens will be sent to the assessor without patients name or HN that can be linked to the treatment received They will be provided only the study ID number in which only the principle investigator can link it to the treatment received
The main outcome is HPV clearance It is measured by the gold-standard HPV testing This will be performed at baseline and 12 months later
Data analysis
There were two main parts of analysis - describing selected characteristics of the study patients and analysis for answering the research questions The first part selected baseline characteristics of the patients in each treatment were compared ie age sex sexual experiences underlying diseases etc Comparability of the distribution of those selected characteristics based on judgment rather than statistical significant tests In this part proportion was use for summarizing categorical data For continuous data the statistics include mean standard deviation minimum maximum and median
For the second part the analysis was based on the group in which the study patients were randomized intention-to-treat basis The different rate of clearance between the two arms of the trial and its 95 confidence interval will be calculated This will be done at 12 months after the treatment Z-test will be used for testing if such differences are different from zero Multiple logistic regression will be used to control effects of any important confounding factors Absolute risk reduction ARR relative risk reduction RRR and number needed to treat NNT will also be calculated
The statistical analysis of this clinical trial will be performed based on intention-to-treat principle All hypothesis tests are two-tailed at significant level of 005 Statistical package for all analysis is STATA version 100
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None