Trial Outcomes & Findings for Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR) (NCT NCT00405704)

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

607 participants

Primary outcome timeframe

2 years

Results posted on

2020-04-21

Participant Flow

Participant milestones

Participant milestones
Measure	Trimethoprim-Sulfamethoxazole Trimethoprim-Sulfamethoxazole: Cherry-flavored liquid suspension with 3 mg of trimethoprim plus 15 mg sulfamethoxazole per kilogram of body weight, taken once daily.	Placebo Placebo: Cherry flavored liquid suspension matched to active comparator.
Overall Study STARTED	302	305
Overall Study Completed Outcome Renal Scan	227	235
Overall Study Completed Assessments for New Scarring	220	227
Overall Study Outcome Stool Assessed	203	210
Overall Study Recurrent UTI With E. Coli	30	57
Overall Study Recurrent UTI With TMP-SMZ Panel	38	69
Overall Study COMPLETED	261	259
Overall Study NOT COMPLETED	41	46

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Trimethoprim-Sulfamethoxazole n=302 Participants Trimethoprim-Sulfamethoxazole: Cherry-flavored liquid suspension with 3 mg of trimethoprim plus 15 mg sulfamethoxazole per kilogram of body weight, taken once daily.	Placebo n=305 Participants Placebo: Cherry flavored liquid suspension matched to active comparator.	Total n=607 Participants Total of all reporting groups
Age, Continuous	12 months n=5 Participants	12 months n=7 Participants	12 months n=5 Participants
Sex: Female, Male Female	277 Participants n=5 Participants	281 Participants n=7 Participants	558 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants	24 Participants n=7 Participants	49 Participants n=5 Participants
Region of Enrollment United States	302 participants n=5 Participants	305 participants n=7 Participants	607 participants n=5 Participants

PRIMARY outcome

Timeframe: 2 years

Outcome measures

Outcome measures
Measure	Trimethoprim-Sulfamethoxazole n=302 Participants Trimethoprim-Sulfamethoxazole: Cherry-flavored liquid suspension with 3 mg of trimethoprim plus 15 mg sulfamethoxazole per kilogram of body weight, taken once daily.	Placebo n=305 Participants Placebo: Cherry flavored liquid suspension matched to active comparator.
Recurrent Febrile or Symptomatic Urinary Tract Infection During 2-year Follow-up	39 participants	72 participants

SECONDARY outcome

Timeframe: 2 years

Population: The analysis population excluded 75 subjects in the trimethoprim-sulfamethoxazole group and 70 subjects in the placebo group who did not have an outcome dimercaptosuccinic acid scan.

Renal scarring was defined as a decreased uptake of tracer that was associated with loss of contours or the presence of cortical thinning. Outcome dimercaptosuccinic acid (DMSA) scan was performed at 2 years after enrollment or 3-4 months after the child had met treatment failure criteria.

Outcome measures

Outcome measures
Measure	Trimethoprim-Sulfamethoxazole n=227 Participants Trimethoprim-Sulfamethoxazole: Cherry-flavored liquid suspension with 3 mg of trimethoprim plus 15 mg sulfamethoxazole per kilogram of body weight, taken once daily.	Placebo n=235 Participants Placebo: Cherry flavored liquid suspension matched to active comparator.
Outcome Renal Scarring	27 participants	24 participants

SECONDARY outcome

Timeframe: 2 years

Population: The analysis population excluded 75 subjects in the trimethoprim-sulfamethoxazole group and 70 subjects in the placebo group who did not have an outcome dimercaptosuccinic acid scan.

Severe renal scarring was defined as scarring in more than 4 of 12 segments in at least one kidney or global atrophy characterized by diffusely scarred and shrunken kidney. Outcome DMSA scan performed at 2 years after enrollment or 3-4 months after the child had met treatment failure criteria.

Outcome measures

Outcome measures
Measure	Trimethoprim-Sulfamethoxazole n=227 Participants Trimethoprim-Sulfamethoxazole: Cherry-flavored liquid suspension with 3 mg of trimethoprim plus 15 mg sulfamethoxazole per kilogram of body weight, taken once daily.	Placebo n=235 Participants Placebo: Cherry flavored liquid suspension matched to active comparator.
Severe Renal Scarring on Outcome Scan	9 participants	6 participants

SECONDARY outcome

Timeframe: 2 years

Population: The analysis population excluded 82 subjects in the trimethoprim-sulfamethoxazole group and 78 subjects in the placebo group who did not have an outcome dimercaptosuccinic acid scan.

New renal scarring was defined as scarring on the outcome renal scan with technetium -99m-labeled dimercaptosuccinic acid that was not present at baseline. Outcome DMSA scan performed at 2 years after enrollment or 3-4 months after the child had met treatment failure criteria.

Outcome measures

Outcome measures
Measure	Trimethoprim-Sulfamethoxazole n=220 Participants Trimethoprim-Sulfamethoxazole: Cherry-flavored liquid suspension with 3 mg of trimethoprim plus 15 mg sulfamethoxazole per kilogram of body weight, taken once daily.	Placebo n=227 Participants Placebo: Cherry flavored liquid suspension matched to active comparator.
New Renal Scarring on Outcome Scan	18 participants	19 participants

SECONDARY outcome

Timeframe: 2 years

Treatment failure was defined as the occurrence of two febrile urinary tract infections (UTIs), one febrile UTI and three symptomatic UTIs, four symptomatic UTIs, or new or worsening renal scarring on an interim scan (e.g,, the 12-month visit); renal scans from the 2-year visit are NOT considered in the treatment failure criteria.

Outcome measures

Outcome measures
Measure	Trimethoprim-Sulfamethoxazole n=302 Participants Trimethoprim-Sulfamethoxazole: Cherry-flavored liquid suspension with 3 mg of trimethoprim plus 15 mg sulfamethoxazole per kilogram of body weight, taken once daily.	Placebo n=305 Participants Placebo: Cherry flavored liquid suspension matched to active comparator.
Treatment Failure Composite	14 participants	27 participants

SECONDARY outcome

Timeframe: 2 years

Population: The analysis population excluded 99 subjects in the trimethoprim-sulfamethoxazole group and 95 subjects in the placebo group who did not have stool analyzed at the outcome visit.

Outcome measures

Outcome measures
Measure	Trimethoprim-Sulfamethoxazole n=203 Participants Trimethoprim-Sulfamethoxazole: Cherry-flavored liquid suspension with 3 mg of trimethoprim plus 15 mg sulfamethoxazole per kilogram of body weight, taken once daily.	Placebo n=210 Participants Placebo: Cherry flavored liquid suspension matched to active comparator.
Presence of E.Coli Resistant to Trimethoprim-Sulfamethoxazole (TMP-SMZ) (Based on Rectal Swab)	56 participants	41 participants

SECONDARY outcome

Timeframe: 2 years

Population: The analysis population is restricted to the 30 subjects in the trimethoprim-sulfamethoxazole (TMP-SMZ) group and 57 subjects in the placebo group who had a recurrent UTI with E. coli for which sensitivity to TMP-SMZ was assessed.

Outcome measures

Outcome measures
Measure	Trimethoprim-Sulfamethoxazole n=30 Participants Trimethoprim-Sulfamethoxazole: Cherry-flavored liquid suspension with 3 mg of trimethoprim plus 15 mg sulfamethoxazole per kilogram of body weight, taken once daily.	Placebo n=57 Participants Placebo: Cherry flavored liquid suspension matched to active comparator.
Recurrent Febrile or Symptomatic UTI With Resistant E. Coli	19 participants	11 participants

SECONDARY outcome

Timeframe: 2 years

Population: The analysis population is restricted to the 38 subjects in the trimethoprim-sulfamethoxazole (TMP-SMZ) group and 69 subjects in the placebo group who had a recurrent UTI with an organism for which sensitivity to TMP-SMZ was assessed.

Outcome measures

Outcome measures
Measure	Trimethoprim-Sulfamethoxazole n=38 Participants Trimethoprim-Sulfamethoxazole: Cherry-flavored liquid suspension with 3 mg of trimethoprim plus 15 mg sulfamethoxazole per kilogram of body weight, taken once daily.	Placebo n=69 Participants Placebo: Cherry flavored liquid suspension matched to active comparator.
Recurrent Febrile or Symptomatic UTI With Any Resistant Pathogen	26 participants	17 participants

Adverse Events

Trimethoprim-Sulfamethoxazole

Serious events: 0 serious events

Other events: 79 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 105 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Trimethoprim-Sulfamethoxazole n=302 participants at risk Trimethoprim-Sulfamethoxazole: Cherry-flavored liquid suspension with 3 mg of trimethoprim plus 15 mg sulfamethoxazole per kilogram of body weight, taken once daily.	Placebo n=305 participants at risk Placebo: Cherry flavored liquid suspension matched to active comparator.
General disorders Fever	14.2% 43/302 • Number of events 58 • 2 years	18.0% 55/305 • Number of events 80 • 2 years
General disorders Otitis Media	4.3% 13/302 • Number of events 18 • 2 years	7.9% 24/305 • Number of events 33 • 2 years
General disorders Pharyngitis	6.3% 19/302 • Number of events 25 • 2 years	4.6% 14/305 • Number of events 20 • 2 years
General disorders Rash	7.6% 23/302 • Number of events 30 • 2 years	7.5% 23/305 • Number of events 26 • 2 years
General disorders Viral Infection	4.6% 14/302 • Number of events 14 • 2 years	5.2% 16/305 • Number of events 20 • 2 years
General disorders Diarrhea	3.6% 11/302 • Number of events 14 • 2 years	6.2% 19/305 • Number of events 27 • 2 years

Additional Information

Dr. Myra Carpenter, Senior Investigator

UNC Chapel Hill

Phone: 919-962-3245

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place