Please select the eligibility criteria that correspond to the clinical trial below.
Title: The Comparison of the Efficacy of Once and Twice Daily Colchicine Dosage in Pediatric Patients With Familial Mediterranean Fever: A Randomized Trial
Brief Summary: It was aimed to examine the efficacy and safety of once daily dosage schema of colchicine in pediatric patients with FMF compared to twice daily dosage schema.

In this 24-week, multicentric, randomized, controlled, noninferiority trial, pediatric patients newly diagnosed with FMF, carrying homozygote or compound heterozygote mutation and did not receive any treatment, were included. Patients were randomly assigned using block randomization method to receive treatment with once or twice daily doses. Clinical and laboratory characteristics and medication side effects were recorded and compared between groups. The study complied with Good Clinical Practice and the Consolidated Standards for Reporting of Trials (CONSORT) statement.


Options:
A: Inclusion Criteria:

* Diagnosed with Familial Mediterranean Fever according to Yalcinkaya or
* Tel-Hashomer criteria
* Diagnosis confirmed with the genetic analysis as compound heterozygote or
* homozygote mutation
* Patients between ages of 5-16 and weighted 15-30 kg
* Not received any treatment for FMF

Exclusion criteria:

* Major congenital malformation
* Organ transplantation
* Hepatic disorder
* Chronic kidney disease
* AA amyloidosis
* Thyroid disease
* Rheumatologic disorders other than FMF
B: Inclusion Criteria:

A subject must fulfil the following criteria in order to be included in the study:

1. FMF diagnosed as per the Tel-Hashomer criteria -(Criteria for the diagnosis of familial Mediterranean fever. Arthritis Rheum.1998 Aug; 41(8):1516-7-Livneh A, Langevitz P, Zemer D, Zaks N, Kees S, Lidar T, Migdal A, Padeh S, Pras M).
2. 18-65 years of age
3. Verified as mutations in both alleles of the MEFV gene, thus including homozygous and compound heterozygous patients
4. Patient compliant with maximum tolerable dose of colchicine (up to 3 mg/day)
5. At least one FMF attack per month in chest, abdomen or joints (definition of attack see above)
6. Adequate contraception for sexually active male and female patients

Exclusion Criteria:

The presence of any of the following will exclude a subject from inclusion in the study:

1. Patient pregnant at enrolment visit
2. Prior or existing malignancy
3. Active infection
4. Manifest renal failure with Creatinine clearance \<30mL/min as determined by the equation Creatinine clearance (ml/min) = (140-age) x Wight (Kg) /72 x serum creatinine (mg/dcl) For women one should multiply the results by 0.8
5. Live vaccinations last three months before enrolment
6. Sociopsychological state threatening compliance with the treatment protocol
7. Alcohol or substance abuse
8. Concomitant medication with biological or anti-rheumatic disease-modifying drugs or systemic steroids
9. Any prior use of IL-1 inhibitory drugs
10. Associated disease that could interfere with clinical assessment:

    1. Rheumatic disorder
    2. Systemic disease, e.g. autoimmune or other autoinflammatory disorder, diabetes, hypertension, vasculitis, Behçet's disease
    3. Gastrointestinal disorder, e.g. Crohn's disease, ulcerative colitis, irritable bowel syndrome
    4. Cardiovascular disorder, e.g. post myocardial infarction, angina
    5. Pulmonary disorder, e.g. COPD, pulmonary hypertension
    6. Any other condition which in the opinion of the investigator makes the subject unsuitable for inclusion
11. Enrolment in another concurrent clinical study, or intake of an investigational drug, within three months prior to inclusion in this study
12. Failure or refusal to cooperate with given instructions

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C: Inclusion Criteria:

* Double-blind phases: adults age 18 and above; Open-label extension: Adults and children aged 7 years and older.
* Was diagnosed with Familial Cold Auto-inflammatory Syndrome (FCAS) or Muckle-Wells Syndrome (MWS) based upon clinical signs and symptoms
* Had documented mutation in NLRP-3 (Cold Induced Autoinflammatory Syndrome-1 or CIAS1) in subject or relative, and willingness to have a confirmatory genetic (Deoxyribonucleic acid or DNA) test (cheek swab).
* Was able to understand and comply with study procedures and was able to provide informed consent
* If female, was not currently pregnant and was willing to use contraception during the study

Exclusion Criteria:

* Had evidence of untreated tuberculosis or other conditions/therapies that made the subject inappropriate for this study.
D: Inclusion Criteria:

* Subject has a definitive diagnosis of FMF as by the Tel-Hashomer clinical criteria (long version of criteria) with at least one mutation on one of the MEFV gene alleles. However, subjects with an isolated heterozygous mutation of exon 2 of the MEFV gene (including E148Q) will not be eligible.
* Subject must have an estimated mean of at least one acute FMF attack per month before and during the month of screening.
* Subject is at least four years of age (with no upper limit of age).
* Subjects must have received an adequate trial of colchicine defined as treatment of at least 1.5 mg/d for at least 3 months if ≥6 years old or 1.2 mg/d if less than 6 years, or an inability to tolerate colchicine due to adverse effects in a dose that controls acute attacks in the frequency of less than one attack per month.
* If subject is being treated with anakinra at the time of consent, washout must be done (about 3 days). Subject must experience 2 attacks before randomization visit can occur.
* If subject has been treated previously with anti-TNF drugs, appropriate washout must be done. Etanercept must be discontinued for 4 weeks prior to randomization; Adalimumab and Infliximab must be discontinued for 8 weeks prior to randomization.
* If subject is a female of childbearing potential, she must agree to use adequate contraception (adequate contraception can include abstinence) for the duration of the trial and 3 months after and must have a negative serum or urine pregnancy test prior to administration of study medication.
* If subject is a male and has reached puberty, he must agree to use adequate contraception or abstinence during the study and for 3 months after discontinuation from study.
* Subject's parent or legal guardian has provided written informed consent prior to screening for this study or if subject is older than 18 years has provided informed consent him/herself.
* Subject, if applicable, has assented to participate prior to screening for this study.
* Subject and, if applicable, parent/legal guardian, agree to comply with study requirements and are able to come to the clinic for all required study visits.

Exclusion Criteria:

* The subject has existing biopsy proven amyloidosis or proteinuria \>0.5 gram per day.
* The subject has another active inflammatory rheumatic disease.
* The subject has an active malignancy of any type, or history of a malignancy.
* The subject has active GI disease (e.g., inflammatory bowel disease), a chronic or acute renal or hepatic disorder, or a significant coagulation defect.
* The subject has an AST (SGOT), ALT (SGPT) or BUN \>2 x ULN or creatinine \>1.5 mg/dL or any other laboratory abnormality considered by the examining physician to be clinically significant within 28 days before the Baseline visit.
* Current use of an anti-tumor necrosis factor drug.
* The subject has, in the investigator's opinion, a chronic condition (e.g., diabetes, epilepsy) that is either not stable or well-controlled and may interfere with the conduct of the study.
* The subject has received any investigational medication within 30 days before the first dose of study medication or is scheduled to receive an investigational drug, other than study medications described in this protocol, during the course of the study.
* The subject has chronic or active infection or any major episode of infection requiring hospitalization or treatment with i.v. antibiotics within 30 days or oral antibiotics within 14 days prior to the screening evaluation.
* The subject has known positive human immunodeficiency virus (HIV) status.
* The subject has known past or current hepatitis.
* The subject has received a live virus vaccine within 1 month prior to the baseline visit.
* The subject has a positive PPD test.
* The subject is sexually active and not practicing effective birth control.
* The subject is pregnant or breast feeding a child.
* Any concurrent medical condition which would, in the investigator's opinion, compromise the subject's ability to tolerate the study drug or would make the subject unable to cooperate with the protocol.
* History of/or current psychiatric illness that would interfere with ability to comply with protocol requirements or give informed consent.
* Subject has a history of alcohol or drug abuse within the past 6 months that would interfere with ability to comply with protocol requirements.
* Inability to comply with the study requirements for any reason.

Answer: A