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):
- Proportion of patients with severe adverse events. Measuring time: one year. - Presence of clinical adverse events (AE) (distribution frequency for the appearance of adverse events (Yes, No), type of event (name of the AE), duration (time between beginning and end of the event), intensity of AE (mild, moderate, severe), relation of causality (remote, possible, probable, very probable), result of AE (recuperate, improvement, persist or sequels), attitude concerning the studied treatment (without changes, dose modification, temporal or definitive treatment discontinuation). Measuring time: one year. - Vital signs (body temperature in degrees Celsius, heart rate in beats per minute, blood pressure in mm Hg and respiratory rate in breaths per minute). Measuring time: before treatment, at 30 minutes, each 4 hours during first 24 hours post-first injection, each 12 hours during first week; at each consultation the rest of the time or at any moment if symptoms. - Electrocardiogram. Measuring time: Before treatment, 12 hours after each administration during first week, and later quarterly during first year if no toxicity signs or at any moment if symptoms. - Echocardiogram. Measuring time: Before treatment, 12 hours after each administration during first week, and later quarterly during first year if no toxicity signs or at any moment if symptoms. - Laboratory tests (complete blood count, platelet count, coagulation least ASAT, ALAT, FAL, LDH, creatinine, glucose, total protein, albumin, CPK, electrolytes). Measuring time: week 0, week 1 (before 3rd application), monthly during first 3 months, quarterly during first year and biannually during follow-up (until to complete 5 years). - Proportion of patients that develop anti-IFN antibodies. Measuring time: week 0 and quarterly until to complete the treatment.
Key secondary outcomes:
- Serum alpha Interferon and gamma Interferon concentrations. Measuring time: Baseline, 1, 3, 6, 12, 24, 48, 72 and 96 hours after first injection. - Serum neopterin. Measuring time: Baseline and 6, 12, 24, 48, 72 and 96 hours after first injection. - Serum beta2-microglobulin. Measuring time: Before and 6, 12, 24, 48, 72 and 96 hours after first injection. - 2',5' oligoadenylate synthetase (2',5' OAS) mRNA expression in peripheral blood. Measuring time: Baseline, 6, 12, 24, 48, 72 and 96 hours after first injection. - Molecular (mRNA STAT-1 levels, FasL, FasR, Caspase). Measuring time: Baseline, 6, 12, 24, 48, 72 and 96 hours after first injection. - Clinical response of the lesions (according to SWAT severity criteria). Measuring time: week 0, monthly during the first trimester, quarterly rest of the year, and biannually during follow-up (until to complete 5 years). - Time to reach clinical response. Measuring time: biannually during treatment and follow-up (until to complete 5 years). - Time of duration of the clinical response. Measuring time: biannually during treatment and follow-up (until to complete 5 years). - Disease-free interval. Measuring time: biannually during treatment and follow-up (until to complete 5 years). - 5-years survival. Measuring time: biannually during treatment and follow-up. - Mean time of survival - 5-years progression. Measuring time: biannually during treatment and follow-up. - Mean time for progression - Quality of life. Measuring time: week 0, months 3, 6, 9 and 12, and biannually during follow-up (until to complete 5 years).