Section to complete information about primary and secondary outcomes including. It includes the metric or method of measurement used and, the time point for every outcome.
Primary outcome(s):
Global Response (Integrated evaluation of colposcopy, histologic and virological response. Categories: Complete response, Partial response, Stable Disease and Progressive disease). Measurement time: at the fourth month of the patients included and, 9 months (a month after end of treatment). The categories will analyze as:
- Complete Response-RC (Colposcopy [Disappearance of the initial lesion and no new lesions appear] Histology [Disappearance of the initial lesion No degree of Cervical intraepithelial Neoplasia (CIN)] Virological [Viral genotype: Negative Human Papillomavirus (HPV) detection high or low oncogenic risk and Viral load: Not detectable]).
- Partial Response-RP (Colposcopy [Reduction between 30 to 50% or more of the initial lesion and no new lesions appear] Histology [Reduction of CIN to one degree or more] Virological [Viral genotype: No detection of viral genotypes of high oncogenic risk (16, 18, 31, 33, 45, 52 and 58) identified in the initial examination, but positive to HPV of low oncogenic risk Viral load: Reduction of the value of the viral load in at least one base logarithm 10] It will be considered partial when at least two of the response variables are present, genotype and viral load variables will always be present).
- Stable disease-EE (Colposcopy [Same morphometry or reduction of less than 30% of the initial lesion] Histology [Same degree of initial lesion is maintained] Virology [Viral genotype: Initial genotypes are maintained Viral load: Equal result than the initial examination, no change in the viral load values.] It will be considered a stable disease when at least two of the response variables are present).
- Progressive Disease-EP (Colposcopy [Increase in the diameter of the lesion The lesion extends to one or more quadrants that were not in the initial lesion.] Histology [Increase in one degree of the lesion of CIN or presence of histological signs of invasion] Virology [Viral genotype: Initial genotypes or appearance of one or more oncogenic genotypes are maintained Viral load: Initial genotypes show an increase in viral load value in at least one base 10 logarithm. Other oncogenic genotypes appear with viral load values greater than or equal to 103 copies / ml.] It will be considered progressive disease when at least two of the response variables are present.The variable viral load will always be present).
Key secondary outcomes:
Related to the response
1- Colposcopy response (Complete Response: Disappearance of the initial lesion and no new lesions appear; Partial Response: Reduction between 30 to 50% or more of the initial lesion and no new lesions appear; Stable Disease: Equal morphometry or minor reduction 30% of the initial lesion; Progressive Disease: Increased diameter of the lesion The lesion extends to one or more quadrants that were not in the initial lesion). Measurement time: At baseline, at 4 months after starting the treatment and, at 9 months (a month after end of treatment).
2- Histological Response (Complete Response: Disappearance of initial injury No degree of CIN; Partial Response: Reduction of CIN to one degree or more; Stable Illness: Same degree of initial injury remains; Progressive Disease: Increase by one degree lesion of CIN or presence of histological signs of invasion). Measurement time: At baseline, at 4 months after starting the treatment and, at 9 months (a month after end of treatment).
3- Virological response (Complete response: Viral genotype: Negative result for the detection of human papillomavirus (HPV) with high or low oncogenic risk and Viral load: Not detectable; Partial response: Viral genotype: No detection of viral genotypes of high oncogenic risk (16, 18, 31 , 33, 45, 52 and 58) identified in the initial examination, but positive to HPV of low oncogenic risk and viral load: Reduction of the value of the viral load in at least one logarithm of base 10; Stable Disease: Viral genotype: Se maintain the initial genotypes and viral load: Same result as the initial examination, no change in the viral load values; Progressive Disease: Viral genotype: The initial genotypes are maintained or the appearance of one or more oncogenic genotypes and viral load: genotypes initials show an increase in the viral load value in at least one logarithm of base 10. Other oncogenic genotypes appear with viral load values greater than or equal to 103 copies/ml). Measurement time: At baseline, at 4 months after starting the treatment and, at 9 months (a month after end of treatment).
Related to security
4- Adverse Events (AE). Measurement time: At baseline, at 4 months after starting the treatment and, at 9 months (a months after finished the treatment). The AE will measure as:
-Occurrence of an AE in the patient (Yes/No)
-Description of the AE (Name of the AE presented)
-Duration of the AE (Difference of dates between the start and end of the AE)
-Intensity of the AE (Classification according to CECMED Regulation 45/2007 in: Mild, Moderate, and Severe)
-Gravity of AE (Serious or Not serious. Considering serious adverse events those that: 1.Produce the patient’ death, 2.Life-threatening, 3.Hospitalization or prolongation of hospitalization indicated, 4. Produce significant or persistent disability, 5.Produce birth defect or congenital anomaly)
-Attitude respect to the treatment under study (No changes, Dose modification, Temporary interruption of the treatments under study, Definitive interruption of the treatments under study).
-Result of the EA (Recovered, improved, persists or sequels)
-Causality Relationship (Definitive, Very likely, Probable, Possible, Not related, Unknown)
