Trial Title:
Validation of Advanced Colorectal Neoplasm Risk Categories in a Prospective Cohort in Mexico
NCT ID:
NCT05661292
Condition:
Colorectal Cancer Screening
Conditions: Official terms:
Neoplasms
Colorectal Neoplasms
Conditions: Keywords:
Colorectal cancer
Screening
Mexico
Study type:
Observational
Overall status:
Recruiting
Study design:
Time perspective:
Prospective
Intervention:
Intervention type:
Diagnostic Test
Intervention name:
Fecal inmunochemical test
Description:
A fecal inmunochemical test will be performed prior to colonoscopy.
Other name:
FIT
Intervention type:
Diagnostic Test
Intervention name:
Colonoscopy
Description:
A colonoscopy will be performed. Any polyp identified will be resected (polypectomy) and
analyzed histologically. NOTE: The subject and colonoscopist will be blinded to FIT test
results and risk category.
Intervention type:
Biological
Intervention name:
Optional collection of tissue, blood and urine for future biomedical research
Description:
Subjects may optionally participate in the collection of tissue, blood, and urine samples
for future biomedical research. This procedure consists of taking a 15 ml sample of
venous blood and 20 ml of urine. The tissue samples to be used will be those that have
been taken for diagnostic purposes during the colonoscopy. Additional biopsies not
required for medical care will not be taken. These samples will be used as long as they
are no longer required to establish a diagnosis.
Other name:
Tissue, blood and urine
Summary:
Worldwide, there are 1,361,000 new cases of colorectal cancers (CRC) annually, with
694,000 deaths. However, the incidence varies by up to a factor of 10x between high and
low incidence countries (eg. USA vs Mexico, incidence rate of 42.54 vs 7.44 / 100,000
inhabitants). Mexico is considered a low-incidence country, with 8,651 new cases and
4,694 deaths annually.
CRC is a preventable and detectable disease. Screening programs established in
high-incidence countries have managed to reduce the incidence and mortality from this
disease and it is considered a cost-effective strategy. In less developed countries where
there are no screening programs for CRC, the highest number of deaths occurs despite
having the lowest number of cases. It is recognized that a barrier to establishing a
screening program in a country with low incidence and limited resources is
cost-effectiveness.
The prevalence of Advanced Colorectal Neoplasia (ACN) detected by screening colonoscopy
in a Mexican cohort of 1172 INNSZ patients was 2.9%. In the US the prevalence is 7.6%.
The number of colonoscopies to be performed to detect ACN was estimated at 34 for Mexico
and 13 for the US, which suggests that the cost-effectiveness of screening colonoscopy
could be 3 times lower in our country.
In Mexico there is no national screening program for CRC. The eligible population (adults
between 50 and 75 years old) for CRC screening is estimated in 20 million of Mexicans. It
is recognized that Mexico does not have enough financial resources nor the infrastructure
to screen the entire eligible population either by direct colonoscopy, or by FIT (fecal
immunochemical test) followed by colonoscopy. With a 5% frequency of positive FIT, nearly
1,000,000 follow-up colonoscopies would be required annually in a population screening
program.
An alternative could be to offer screening based on risk, which means only offering
screening to the highest-risk population.
There are calculators to predict the risk of identifying ACN in a screening colonoscopy,
however, none have been developed and validated in the Mexican population. The weight of
the risk factors associated with ACN in the Mexican population could be different, so it
is necessary to develop and validate an ACN risk calculator that allows the Mexican
population to be stratified and to concentrate screening efforts on the population at
highest risk.
Detailed description:
This is a prospective cohort of subjects eligible for CRC screening in Mexico City.
The main goal is to validate the APCS clinical score as a risk - stratification tool for
screening colonoscopy in a Mexican population.
The Asian-Pacific Colorectal Screening (APCS) score is a clinical tool used to stratify
subjects according to the probability of identification of Advanced Colorectal Neoplasia
(ACN) in a screening colonoscopy. ACN includes lesions larger than 10 mm with one or more
of the following: a villous content, high-grade dysplasia, or carcinoma. The tool
stratifies the population into three risk categories, considering: age, sex, smoking
history, and first-degree family history of colorectal cancer. The total score obtained
allows the stratification into average risk (0-1 point), moderate (2-3 points), and high
risk (4-7 points). The prevalence of ACN in the original validation cohort of the APCS
was 1.3% for average risk, 3.2% in moderate risk and 5.2% in high risk.
Investigators previously evaluated the APCS score in a retrospective study of screening
colonoscopy in Mexican population (n=1269). The prevalence of ACN was 2.6% vs 5.2%
(p=0.027) for moderate risk and high-risk categories, respectively.
To implement a risk-stratified screening program for the Mexican population, prospective
validation was considered necessary. A prospective study would allow for collection and
evaluation of additional variables that could potentially improve APCS score. FIT cut-off
values have never been validated in Mexican population and are required to implement a
national colorectal screening program. Prospective design will also allow for bio banking
for future medical research.
The following procedures will be performed:
1. Subjects will be invited to participate in the study, and if they accept, an
informed consent will be given and explained to them. They will have a standardized
interview dedicated to promoting CRC screening and complete a CRC risk factor
questionnaire to determine their risk category.
2. Subjects may optionally participate in the collection of tissue, blood, and urine
samples for future biomedical research. This procedure consists of taking a 15 ml
sample of venous blood and 20 ml of urine. The tissue samples to be used will be
those that have been taken for diagnostic purposes during the colonoscopy.
Additional biopsies not required for medical care will not be taken. These samples
will be used as long as they are no longer required to establish a diagnosis.
3. A Fecal Immunochemical Test (FIT) will be performed prior to the colonoscopy. Note:
A positive FIT will have a Hb value >20 ug/g of stool.
4. A colonoscopy will be performed. Any polyp identified will be resected (polypectomy)
and analyzed histologically. NOTE: The subject and physician will be blinded to FIT
test results and risk category.
In subsequent medical consultation, the results of the risk score, the FIT test, and
colonoscopy will be discussed.
5. If the patient does not perform any of the tests, they will be interviewed on a
second occasion to complete a questionnaire of reasons of rejection. NOTE: It is
anticipated that a proportion of subjects will verbally accept the screening, but
the proposed tests will not be carried out (this will measure the percentage of
acceptance of the recommendation).
Given that age and gender are the most important risk factors, the population will be
stratified simulating the Mexican population pyramid as follows: 50% male subjects and
50% female subjects. By age groups: 50-54 years (31%), 55-59 (24%), 60-64 (19%), 65-69
(14%), 70-75 (12%).
The data collected from the participants will be entered into an electronic registry
(Redcap) in real-time. A periodic review of the electronic registry will be carried out
by personal of the protocol to ensure the quality of the information and that it is
complete. The study does not contemplate external monitoring of the data.
Statistical considerations
- Sample size: for a difference in proportions of 2.6% (prevalence of ACN 5.2% vs.
2.6% in the high vs. moderate-risk population), 868 subjects per group are required
to achieve a power of 80%, with a confidence level of 95 %, that is, 1736 subjects.
It is anticipated that in 15% of the subjects the two screening tests will not be
available, so a total sample of 2000 subjects is proposed.
- Statistical proportions, means, and medians will be used to describe the population.
The differences in proportions will be analyzed with the X2 test. Using a binary
logistic regression model, variables associated with ACN risk will be identified. A
p < 0.05 will be considered statistically significant. The risk calculator will be
developed using the variables identified in the univariate analysis and differential
weight will be assigned to them according to risk. To determine the optimal cut-off
point in FIT test (ng of hemoglobin per gram of feces): the investigators will use
the distribution of the FIT score for patients with and without premalignant lesions
and/or colorectal cancer to estimate sensitivity and specificity. according to
different cut-off values. Subsequently, the investigators will use a decision model
based on specificity/sensitivity ROC curves and according to different FIT cut-off
points. The closer the ROC curve is to the upper left corner, the higher the
predictive power of detecting colorectal lesions.
Criteria for eligibility:
Study pop:
Subjects eligible for CRC screening with or without institutional registry. Subjects with
institutional registry will be identified among patients treated at the Internal Medicine
clinic of the Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán" in
Mexico City. Patients without institutional registry will be identified among relatives
of participants, blood bank, and by diffusion of the protocol with leaflets on social
networks and internal at our center.
Sampling method:
Non-Probability Sample
Criteria:
Inclusion Criteria:
- Asymptomatic subjects between 50 and 75 years of age-eligible for CRC screening with
or without registry at the institute.
Note: concerning symptoms of CRC diagnosis will not be admitted: fresh blood in the
stool, black stools, unexplained weight loss (>10% of usual body weight). Concerning
symptoms of Functional Gastrointestinal Disorder (FGID) will be permitted: loss of
appetite, diarrhea, constipation, abdominal pain or discomfort.
- Subjects who give their informed consent.
- Subjects who have completed the vaccination schedule against the SARS CoV-2 virus
with any of the vaccines approved in Mexico, at least 4 weeks before the
colonoscopy.
Exclusion Criteria:
- Personal history of any type of cancer, except basal cell carcinoma or cervical
cancer in situ.
- Personal history of colon polyps.
- Personal history of abdominal or pelvic radiation due to previous cancer.
- Relatives with familial adenomatous polyposis (FAP) or hereditary non-polyposis CRC.
- Inflammatory bowel disease (IBD).
- High anesthetic risk (ASA greater than 3 of the classification of the American
Society of Anesthesiology).
- Any medical condition that limits life expectancy at the discretion of the
investigator.
- Charlson index > 4.
- Presence of anemia in the last year according to the WHO definition: women <12 g/dl,
men <13 g/dl.
- Previous colectomy.
- Colonoscopy in the previous 5 years.
- Sigmoidoscopy in the previous 3 years.
- A fecal occult blood test in the past year.
- CT colonography in the previous 10 years.
- Clinical data suggestive of CRC such as hematochezia, melena, weight loss greater
than 10% of usual body weight in a 6 months period.
Gender:
All
Minimum age:
50 Years
Maximum age:
75 Years
Healthy volunteers:
Accepts Healthy Volunteers
Locations:
Facility:
Name:
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Address:
City:
Mexico City
Zip:
14080
Country:
Mexico
Status:
Recruiting
Contact:
Last name:
Mónica I Meneses Medina, MD
Phone:
54870900
Phone ext:
2254
Email:
mimm2404@hotmail.com
Contact backup:
Last name:
Vanessa Rosas Camargo, MD
Phone:
54870900
Phone ext:
2254
Email:
dravanessarosascamargo@yahoo.com.mx
Investigator:
Last name:
Fidel D Huitzil Meléndez, MD
Email:
Principal Investigator
Investigator:
Last name:
Vanessa Rosas Camargo, MD
Email:
Sub-Investigator
Investigator:
Last name:
Mónica I Meneses Medina, MD
Email:
Sub-Investigator
Start date:
August 1, 2019
Completion date:
March 30, 2025
Lead sponsor:
Agency:
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Agency class:
Other
Collaborator:
Agency:
Conquer Cancer Foundation
Agency class:
Other
Source:
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05661292
http://globocan.iarc.fr/Default.aspx
https://www.inegi.org.mx/temas/estructura/
