Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR)
Brief Summary: In this 2-year, multisite, randomized, placebo-controlled trial involving 607 children with vesicoureteral reflux that was diagnosed after a first or second febrile or symptomatic urinary tract infecton, we evaluated the efficacy of Trimethoprim-Sulfamethoxazole (TMP-SMZ) prophylaxis in preventing recurrences (primary outcome). Secondary outcomes were renal scarring, treatment failure (a composite of recurrences and scarring), and antimicrobial resistance.


Options:
A: Inclusion Criteria:

* presence of vesico-ureteral reflux (VUR) grade II, III or IV, based on the International Classification, mono or bilateral, diagnosed between one day and 30 months of age after a first episode of acute pyelonephritis, or after birth during diagnostic procedures planned as a consequence of prenatal ultrasonographic evidence of pyelectasia.

Exclusion Criteria:

* previous episodes of urinary tract infection (UTI), even if only suspected (e.g. an episode of fever treated with antibiotics without performing urine culture);
* VUR grade I, because of the high probability of rapid spontaneous resolution;
* VUR grade V, as requested by the Technical Scientific Committee, concerned by the high incidence of associated renal dysplasia;
* recurrence of acute pyelonephritis before the first dimercaptosuccinic acid (DMSA) renal scan, if this was positive for scars.
B: Inclusion Criteria:

* age between 2 months and 6 years,
* normal renal function
* first episode of upper UTI (fever, 2 consecutive positive urinalysis, later confirmed by 2 cultures and high blood inflammation indices)

Exclusion Criteria:

* documented previous urinary tract malformation (prenatal ultrasound)
* seriously compromised general conditions (such as sepsis or vomit)
* hypersensitivity to the antibiotics considered.
C: Inclusion Criteria:

* Age between 2 months and 6 years
* Creatinine clearance (calculated according to Schwartz)  70 ml/min/1.73 m2 (for children in their first year of life, serum creatinine levels within normal range for age and sex)
* First documented upper UTI (diagnostic criteria in Table 1)
* Imaging Diagnostic work-up completed (Table 2) with at least the presence of an acute lesion at the DMSA scan and or a primary non severe reflux ( 1st or 3rd degree)
* Informed consent of parents

Exclusion Criteria:

* Patients with chronic renal insufficiency or  30% relative function of one kidney at DMSA scan
* Patients with urinary tract disorders, such as vesico-ureteral reflux due to complex malformations of the urinary tract, obstruction of the posterior urethra, ureterocele or single kidney, neurogenic bladder
* Patients with reflux  4th degree
* Patients with pyelonephritis that developed during prophylaxis instituted because of prenatal diagnosis of urinary tract dilatation  Hypersensitivity to one of the two selected antimicrobial agents
D: Inclusion Criteria:

* Age at randomization: at least 2 months, but less than 6 years of age. Note that children as young as 1 month were screened for the study.
* Diagnosed first or second febrile or symptomatic UTI within 112 days prior to randomization
* Presence of Grade I- IV VUR based on radiographic voiding cystourethrogram (VCUG) performed within 112 days of diagnosis of index UTI.
* Appropriately treated index febrile or symptomatic UTI

Exclusion Criteria:

* Index UTI diagnosis more than 112 days prior to randomization
* History of more than two UTIs prior to randomization
* For patients less than 6 months of age at randomization, gestational age less than 34 weeks
* Co-morbid urologic anomalies
* Hydronephrosis, SFU Grade 4
* Ureterocele
* Urethral valve
* Solitary kidney
* Profoundly decreased renal size unilaterally on ultrasound (based on 2 standard deviations below the mean for age and length) performed within 112 days after diagnosis of index UTI
* Multicystic dysplastic kidney
* Neurogenic bladder
* Pelvic kidney or fused kidney
* Known sulfa allergy, inadequate renal or hepatic function, Glucose-6-phosphate dehydrogenase deficiency or other conditions that are contraindications for use of TMP-SMZ
* History of other renal injury/disease
* Unable to complete the study protocol
* Congenital or acquired immunodeficiency
* Underlying anomalies or chronic diseases that could potentially interfere with response to therapy such as chronic gastrointestinal conditions (i.e., malabsorption, inflammatory bowel disease), liver or kidney failure, or malignancy.
* Complex cardiac disease as defined in the Manual of Procedures.
* Any known syndromes associated with VUR or bladder dysfunction
* Index UTI not successfully treated
* Unlikely to complete follow-up
* Family history of anaphylactic reaction to sulfa medications

Answer: D