Trial Outcomes & Findings for Losartan for the Treatment of Pediatric NAFLD (NCT NCT03467217)

NCT ID: NCT03467217

Last Updated: 2021-10-21

Results Overview

Change ALT value in U/L (24 weeks minus baseline). A negative score indicates improvement.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

83 participants

Primary outcome timeframe

Baseline and 24 weeks

Results posted on

2021-10-21

Participant Flow

Participant milestones

Participant milestones
Measure	Losartan 100 mg losartan once per day	Placebo Matching placebo, taken once per day
Overall Study STARTED	43	40
Overall Study COMPLETED	33	34
Overall Study NOT COMPLETED	10	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Losartan 100 mg losartan once per day	Placebo Matching placebo, taken once per day
Overall Study Trial stopped early	5	2
Overall Study Clinic closed due to COVID-19 pandemic	5	2
Overall Study Lost to Follow-up	0	2

Baseline Characteristics

Losartan for the Treatment of Pediatric NAFLD

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Losartan Potassium Capsule n=43 Participants Dose will be one 50 mg capsule of losartan per day for one week and then increased to two capsules of 50 mg of losartan per day (100 mg total) for 23 weeks patients with baseline weight ≥ 70 kg to \<150 kg. Losartan potassium: Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype	Placebo Losartan Capsule n=40 Participants Dose will be one 50 mg capsule of placebo losartan per day for one week and then increased to two capsules of 50 mg of placebo losartan per day (100 mg total) for 23 weeks for patients with baseline weight ≥ 70 kg to \<150 kg. Placebo losartan capsule: Matching placebo losartan oral capsule	Total n=83 Participants Total of all reporting groups
Age, Continuous	14 years STANDARD_DEVIATION 2 • n=5 Participants	13 years STANDARD_DEVIATION 2 • n=7 Participants	13 years STANDARD_DEVIATION 2 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	6 Participants n=7 Participants	16 Participants n=5 Participants
Sex: Female, Male Male	33 Participants n=5 Participants	34 Participants n=7 Participants	67 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	33 Participants n=5 Participants	33 Participants n=7 Participants	66 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=5 Participants	7 Participants n=7 Participants	17 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	28 Participants n=5 Participants	25 Participants n=7 Participants	53 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	9 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants
Alanine aminotransferase	115 U/L STANDARD_DEVIATION 50 • n=5 Participants	126 U/L STANDARD_DEVIATION 61 • n=7 Participants	120 U/L STANDARD_DEVIATION 55 • n=5 Participants
Aspartate aminotransferase	59 U/L STANDARD_DEVIATION 26 • n=5 Participants	70 U/L STANDARD_DEVIATION 38 • n=7 Participants	64 U/L STANDARD_DEVIATION 33 • n=5 Participants
Alkaline phosphate	192 U/L STANDARD_DEVIATION 114 • n=5 Participants	202 U/L STANDARD_DEVIATION 99 • n=7 Participants	197 U/L STANDARD_DEVIATION 106 • n=5 Participants
y-Glutamyltransferase	53 U/L STANDARD_DEVIATION 44 • n=5 Participants	51 U/L STANDARD_DEVIATION 28 • n=7 Participants	52 U/L STANDARD_DEVIATION 37 • n=5 Participants
Total bilirubin	0.6 mg/dL STANDARD_DEVIATION 0.3 • n=5 Participants	0.6 mg/dL STANDARD_DEVIATION 0.3 • n=7 Participants	0.6 mg/dL STANDARD_DEVIATION 0.3 • n=5 Participants
Direct bilirubin	0.1 mg/dL STANDARD_DEVIATION 0.1 • n=5 Participants	0.1 mg/dL STANDARD_DEVIATION 0.1 • n=7 Participants	0.1 mg/dL STANDARD_DEVIATION 0.1 • n=5 Participants
Total cholesterol	159 mg/dL STANDARD_DEVIATION 44 • n=5 Participants	155 mg/dL STANDARD_DEVIATION 31 • n=7 Participants	157 mg/dL STANDARD_DEVIATION 38 • n=5 Participants
High-density lipoprotein	39 mg/uL STANDARD_DEVIATION 7 • n=5 Participants	41 mg/uL STANDARD_DEVIATION 9 • n=7 Participants	40 mg/uL STANDARD_DEVIATION 8 • n=5 Participants
Low-density lipoprotein	91 mg/uL STANDARD_DEVIATION 40 • n=5 Participants	92 mg/uL STANDARD_DEVIATION 22 • n=7 Participants	91 mg/uL STANDARD_DEVIATION 32 • n=5 Participants
Triglycerides	158 mg/dL STANDARD_DEVIATION 105 • n=5 Participants	128 mg/dL STANDARD_DEVIATION 58 • n=7 Participants	143 mg/dL STANDARD_DEVIATION 87 • n=5 Participants
Fasting serum glucose	91 mg/dL n=5 Participants	87 mg/dL n=7 Participants	89 mg/dL n=5 Participants
Insulin	29 umol/mL n=5 Participants	38 umol/mL n=7 Participants	32 umol/mL n=5 Participants
Homeostasis model assessment (HOMA) score of insulin resistance	6.5 mg/dL x umol/mL/405 n=5 Participants	8.3 mg/dL x umol/mL/405 n=7 Participants	7.1 mg/dL x umol/mL/405 n=5 Participants
Hemoglobin A1c	5.4 percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.6 • n=5 Participants	5.4 percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.3 • n=7 Participants	5.4 percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.5 • n=5 Participants
Height	165 cm STANDARD_DEVIATION 9 • n=5 Participants	165 cm STANDARD_DEVIATION 9 • n=7 Participants	165 cm STANDARD_DEVIATION 9 • n=5 Participants
Weight	95 kg STANDARD_DEVIATION 17 • n=5 Participants	96 kg STANDARD_DEVIATION 19 • n=7 Participants	95 kg STANDARD_DEVIATION 18 • n=5 Participants
Body-mass index	34 kg/m^2 STANDARD_DEVIATION 5 • n=5 Participants	35 kg/m^2 STANDARD_DEVIATION 5 • n=7 Participants	35 kg/m^2 STANDARD_DEVIATION 5 • n=5 Participants
Mid arm circumference	33 cm STANDARD_DEVIATION 4 • n=5 Participants	33 cm STANDARD_DEVIATION 4 • n=7 Participants	33 cm STANDARD_DEVIATION 4 • n=5 Participants
Waist circumference	108 cm STANDARD_DEVIATION 11 • n=5 Participants	111 cm STANDARD_DEVIATION 11 • n=7 Participants	110 cm STANDARD_DEVIATION 11 • n=5 Participants
Hip circumference	110 cm STANDARD_DEVIATION 11 • n=5 Participants	112 cm STANDARD_DEVIATION 11 • n=7 Participants	111 cm STANDARD_DEVIATION 11 • n=5 Participants
Waist to hip ratio	0.99 ratio STANDARD_DEVIATION 0.06 • n=5 Participants	0.99 ratio STANDARD_DEVIATION 0.06 • n=7 Participants	0.99 ratio STANDARD_DEVIATION 0.06 • n=5 Participants
Systolic blood pressure	121 mmHg STANDARD_DEVIATION 9 • n=5 Participants	119 mmHg STANDARD_DEVIATION 9 • n=7 Participants	120 mmHg STANDARD_DEVIATION 9 • n=5 Participants
Diastolic blood pressure	69 mmHg STANDARD_DEVIATION 6 • n=5 Participants	69 mmHg STANDARD_DEVIATION 6 • n=7 Participants	69 mmHg STANDARD_DEVIATION 6 • n=5 Participants
Pulse	79 beats per minute STANDARD_DEVIATION 13 • n=5 Participants	80 beats per minute STANDARD_DEVIATION 13 • n=7 Participants	79 beats per minute STANDARD_DEVIATION 13 • n=5 Participants
Breath rate	18 breaths/minute STANDARD_DEVIATION 3 • n=5 Participants	19 breaths/minute STANDARD_DEVIATION 4 • n=7 Participants	19 breaths/minute STANDARD_DEVIATION 3 • n=5 Participants
Hemoglobin	14.5 g/dL STANDARD_DEVIATION 1.1 • n=5 Participants	14.0 g/dL STANDARD_DEVIATION 1.2 • n=7 Participants	14.2 g/dL STANDARD_DEVIATION 1.2 • n=5 Participants
Hematocrit	43.2 percentage of hematocrit STANDARD_DEVIATION 3.3 • n=5 Participants	42.0 percentage of hematocrit STANDARD_DEVIATION 3.4 • n=7 Participants	42.6 percentage of hematocrit STANDARD_DEVIATION 3.4 • n=5 Participants
MCV	84.9 fL STANDARD_DEVIATION 4.4 • n=5 Participants	84.7 fL STANDARD_DEVIATION 3.4 • n=7 Participants	84.8 fL STANDARD_DEVIATION 4.0 • n=5 Participants
White blood cell count (WBC)	7.2 10^3 cells/uL STANDARD_DEVIATION 1.5 • n=5 Participants	8.6 10^3 cells/uL STANDARD_DEVIATION 2.4 • n=7 Participants	7.9 10^3 cells/uL STANDARD_DEVIATION 2.1 • n=5 Participants
Red blood cell count (RBC)	509 million cells/uL STANDARD_DEVIATION 39 • n=5 Participants	496 million cells/uL STANDARD_DEVIATION 37 • n=7 Participants	503 million cells/uL STANDARD_DEVIATION 39 • n=5 Participants
Neutrophils	3541 cells/uL STANDARD_DEVIATION 1123 • n=5 Participants	4231 cells/uL STANDARD_DEVIATION 1867 • n=7 Participants	3869 cells/uL STANDARD_DEVIATION 1552 • n=5 Participants
Lymphocytes	2656 cells/uL STANDARD_DEVIATION 727 • n=5 Participants	3031 cells/uL STANDARD_DEVIATION 1003 • n=7 Participants	2835 cells/uL STANDARD_DEVIATION 884 • n=5 Participants
Monocytes	501 cells/uL STANDARD_DEVIATION 165 • n=5 Participants	578 cells/uL STANDARD_DEVIATION 217 • n=7 Participants	537 cells/uL STANDARD_DEVIATION 194 • n=5 Participants
Eosinophils	297 cells/uL STANDARD_DEVIATION 245 • n=5 Participants	278 cells/uL STANDARD_DEVIATION 249 • n=7 Participants	288 cells/uL STANDARD_DEVIATION 245 • n=5 Participants
Basophils	35 cells/uL STANDARD_DEVIATION 37 • n=5 Participants	65 cells/uL STANDARD_DEVIATION 126 • n=7 Participants	49 cells/uL STANDARD_DEVIATION 91 • n=5 Participants
Platelet	277 1000 cells/mm^3 STANDARD_DEVIATION 57 • n=5 Participants	311 1000 cells/mm^3 STANDARD_DEVIATION 66 • n=7 Participants	293 1000 cells/mm^3 STANDARD_DEVIATION 64 • n=5 Participants
Sodium	140.0 mEq/L STANDARD_DEVIATION 2.0 • n=5 Participants	139.7 mEq/L STANDARD_DEVIATION 2.0 • n=7 Participants	139.9 mEq/L STANDARD_DEVIATION 2.0 • n=5 Participants
Potassium	4.1 mEq/L STANDARD_DEVIATION 0.3 • n=5 Participants	4.2 mEq/L STANDARD_DEVIATION 0.2 • n=7 Participants	4.2 mEq/L STANDARD_DEVIATION 0.3 • n=5 Participants
Chloride	103.9 mEq/L STANDARD_DEVIATION 2.7 • n=5 Participants	102.9 mEq/L STANDARD_DEVIATION 2.5 • n=7 Participants	103.4 mEq/L STANDARD_DEVIATION 2.6 • n=5 Participants
Bicarbonate	24.3 mEq/L STANDARD_DEVIATION 2.5 • n=5 Participants	24.7 mEq/L STANDARD_DEVIATION 2.0 • n=7 Participants	24.4 mEq/L STANDARD_DEVIATION 2.3 • n=5 Participants
Calcium	9.8 mEq/L STANDARD_DEVIATION 0.4 • n=5 Participants	9.8 mEq/L STANDARD_DEVIATION 0.3 • n=7 Participants	9.8 mEq/L STANDARD_DEVIATION 0.3 • n=5 Participants
Blood urea nitrogen	10.9 mg/dL STANDARD_DEVIATION 3.1 • n=5 Participants	10.5 mg/dL STANDARD_DEVIATION 2.5 • n=7 Participants	10.7 mg/dL STANDARD_DEVIATION 2.8 • n=5 Participants
Creatinine	0.56 mg/dL STANDARD_DEVIATION 0.14 • n=5 Participants	0.56 mg/dL STANDARD_DEVIATION 0.13 • n=7 Participants	0.56 mg/dL STANDARD_DEVIATION 0.14 • n=5 Participants
Estimated glomerular filtration rate (eGFR)	156 mL/min/1.73m^2 STANDARD_DEVIATION 19 • n=5 Participants	155 mL/min/1.73m^2 STANDARD_DEVIATION 17 • n=7 Participants	156 mL/min/1.73m^2 STANDARD_DEVIATION 18 • n=5 Participants
Prothrombin time	12.3 seconds STANDARD_DEVIATION 1.3 • n=5 Participants	11.9 seconds STANDARD_DEVIATION 1.3 • n=7 Participants	12.1 seconds STANDARD_DEVIATION 1.3 • n=5 Participants
International normalized ratio (INR)	1.04 ratio STANDARD_DEVIATION 0.07 • n=5 Participants	1.04 ratio STANDARD_DEVIATION 0.08 • n=7 Participants	1.04 ratio STANDARD_DEVIATION 0.07 • n=5 Participants
Uric acid	6.6 mg/dL STANDARD_DEVIATION 1.7 • n=5 Participants	6.6 mg/dL STANDARD_DEVIATION 1.5 • n=7 Participants	6.6 mg/dL STANDARD_DEVIATION 1.6 • n=5 Participants
C-reactive protein	3.8 mg/L STANDARD_DEVIATION 2.5 • n=5 Participants	3.8 mg/L STANDARD_DEVIATION 3.0 • n=7 Participants	3.8 mg/L STANDARD_DEVIATION 2.7 • n=5 Participants
Time from liver biopsy	0.7 years STANDARD_DEVIATION 0.6 • n=5 Participants	0.8 years STANDARD_DEVIATION 0.6 • n=7 Participants	0.8 years STANDARD_DEVIATION 0.6 • n=5 Participants
Nonalcoholic fatty liver disease (NAFLD) activity score	4.6 units on a scale STANDARD_DEVIATION 1.5 • n=5 Participants	4.4 units on a scale STANDARD_DEVIATION 1.2 • n=7 Participants	4.5 units on a scale STANDARD_DEVIATION 1.4 • n=5 Participants
Steatohepatitis Diagnosis NAFLD, not NASH	15 Participants n=5 Participants	9 Participants n=7 Participants	24 Participants n=5 Participants
Steatohepatitis Diagnosis Borderline Zone 3	9 Participants n=5 Participants	7 Participants n=7 Participants	16 Participants n=5 Participants
Steatosis 5-33%	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Steatohepatitis Diagnosis Borderline Zone 1	11 Participants n=5 Participants	12 Participants n=7 Participants	23 Participants n=5 Participants
Steatohepatitis Diagnosis Definite steatohepatitis	8 Participants n=5 Participants	12 Participants n=7 Participants	20 Participants n=5 Participants
Fibrosis stage Stage 0	17 Participants n=5 Participants	7 Participants n=7 Participants	24 Participants n=5 Participants
Fibrosis stage Stage 1	13 Participants n=5 Participants	20 Participants n=7 Participants	33 Participants n=5 Participants
Fibrosis stage Stage 2	8 Participants n=5 Participants	5 Participants n=7 Participants	13 Participants n=5 Participants
Fibrosis stage Stage 3	5 Participants n=5 Participants	8 Participants n=7 Participants	13 Participants n=5 Participants
Hepatocellular ballooning grade 0 - None	31 Participants n=5 Participants	27 Participants n=7 Participants	58 Participants n=5 Participants
Hepatocellular ballooning grade 1 - Few	6 Participants n=5 Participants	10 Participants n=7 Participants	16 Participants n=5 Participants
Hepatocellular ballooning grade 2 - Many	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Steatosis 34-66%	13 Participants n=5 Participants	11 Participants n=7 Participants	24 Participants n=5 Participants
Steatosis >66%	26 Participants n=5 Participants	23 Participants n=7 Participants	49 Participants n=5 Participants
Lobular inflammation <2 under 20x magnification	21 Participants n=5 Participants	17 Participants n=7 Participants	38 Participants n=5 Participants
Lobular inflammation 2-4 under 20x magnification	16 Participants n=5 Participants	21 Participants n=7 Participants	37 Participants n=5 Participants
Lobular inflammation >4 under 20x magnification	6 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants
Portal inflammation None	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Portal inflammation Mild	30 Participants n=5 Participants	28 Participants n=7 Participants	58 Participants n=5 Participants
Portal inflammation More than mild	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 24 weeks

Population: Results based on complete case analysis.

Change ALT value in U/L (24 weeks minus baseline). A negative score indicates improvement.

Outcome measures

Outcome measures
Measure	Losartan Potassium Capsule n=33 Participants Dose will be one 50 mg capsule of losartan per day for one week and then increased to two capsules of 50 mg of losartan per day (100 mg total) for 23 weeks patients with baseline weight ≥ 70 kg to \<150 kg. Losartan potassium: Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype	Placebo Losartan Capsule n=34 Participants Dose will be one 50 mg capsule of placebo losartan per day for one week and then increased to two capsules of 50 mg of placebo losartan per day (100 mg total) for 23 weeks for patients with baseline weight ≥ 70 kg to \<150 kg. Placebo losartan capsule: Matching placebo losartan oral capsule
Change in Serum Alanine Aminotransferase (ALT) From Baseline.	-5.3 U/L Standard Deviation 51.4	-6.3 U/L Standard Deviation 77.5

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Change from baseline in gamma-glutamyl transpeptidase (GGT), measured in U/L.

Outcome measures

Outcome measures
Measure	Losartan Potassium Capsule n=33 Participants Dose will be one 50 mg capsule of losartan per day for one week and then increased to two capsules of 50 mg of losartan per day (100 mg total) for 23 weeks patients with baseline weight ≥ 70 kg to \<150 kg. Losartan potassium: Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype	Placebo Losartan Capsule n=34 Participants Dose will be one 50 mg capsule of placebo losartan per day for one week and then increased to two capsules of 50 mg of placebo losartan per day (100 mg total) for 23 weeks for patients with baseline weight ≥ 70 kg to \<150 kg. Placebo losartan capsule: Matching placebo losartan oral capsule
Change in Gamma-glutamyl Transpeptidase (GGT) Compared to Baseline	-1.9 U/L Standard Deviation 13.9	0.6 U/L Standard Deviation 19.7

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Change from baseline in serum aspartate aminotransferase, measured in U/L.

Outcome measures

Outcome measures
Measure	Losartan Potassium Capsule n=33 Participants Dose will be one 50 mg capsule of losartan per day for one week and then increased to two capsules of 50 mg of losartan per day (100 mg total) for 23 weeks patients with baseline weight ≥ 70 kg to \<150 kg. Losartan potassium: Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype	Placebo Losartan Capsule n=34 Participants Dose will be one 50 mg capsule of placebo losartan per day for one week and then increased to two capsules of 50 mg of placebo losartan per day (100 mg total) for 23 weeks for patients with baseline weight ≥ 70 kg to \<150 kg. Placebo losartan capsule: Matching placebo losartan oral capsule
Change in Serum Aspartate Aminotransferase AST at 24 Weeks Compared to Baseline AST	0.2 U/L Standard Deviation 27.2	-4.5 U/L Standard Deviation 37.0

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Relative change from baseline in serum ALT, measured in percentage of change.

Outcome measures

Outcome measures
Measure	Losartan Potassium Capsule n=33 Participants Dose will be one 50 mg capsule of losartan per day for one week and then increased to two capsules of 50 mg of losartan per day (100 mg total) for 23 weeks patients with baseline weight ≥ 70 kg to \<150 kg. Losartan potassium: Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype	Placebo Losartan Capsule n=34 Participants Dose will be one 50 mg capsule of placebo losartan per day for one week and then increased to two capsules of 50 mg of placebo losartan per day (100 mg total) for 23 weeks for patients with baseline weight ≥ 70 kg to \<150 kg. Placebo losartan capsule: Matching placebo losartan oral capsule
Relative Change in Serum Alanine Aminotransferase (ALT) Compared to Baseline ALT	2.7 percentage of change Standard Deviation 43.8	-5.7 percentage of change Standard Deviation 73.2

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Change from baseline in ALT at 12 weeks, measured in U/L.

Outcome measures

Outcome measures
Measure	Losartan Potassium Capsule n=33 Participants Dose will be one 50 mg capsule of losartan per day for one week and then increased to two capsules of 50 mg of losartan per day (100 mg total) for 23 weeks patients with baseline weight ≥ 70 kg to \<150 kg. Losartan potassium: Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype	Placebo Losartan Capsule n=34 Participants Dose will be one 50 mg capsule of placebo losartan per day for one week and then increased to two capsules of 50 mg of placebo losartan per day (100 mg total) for 23 weeks for patients with baseline weight ≥ 70 kg to \<150 kg. Placebo losartan capsule: Matching placebo losartan oral capsule
Change in ALT at 12 Weeks Compared to Baseline ALT	-5.8 mg/dL Standard Deviation 43.0	-19.3 mg/dL Standard Deviation 38.5

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Homeostasis Model Assessment of Insulin Resistance Index (HOMA-IR) measures insulin resistance, calculated by fasting insulin (umol/mL) multiplied by fasting glucose (mg/dL), and divided by a constant (405). A higher score indicates higher insulin resistance.

Outcome measures

Outcome measures
Measure	Losartan Potassium Capsule n=33 Participants Dose will be one 50 mg capsule of losartan per day for one week and then increased to two capsules of 50 mg of losartan per day (100 mg total) for 23 weeks patients with baseline weight ≥ 70 kg to \<150 kg. Losartan potassium: Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype	Placebo Losartan Capsule n=34 Participants Dose will be one 50 mg capsule of placebo losartan per day for one week and then increased to two capsules of 50 mg of placebo losartan per day (100 mg total) for 23 weeks for patients with baseline weight ≥ 70 kg to \<150 kg. Placebo losartan capsule: Matching placebo losartan oral capsule
Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Compared to Baseline.	4.5 mg/dL x uU/mL/405 Standard Deviation 8.1	1.1 mg/dL x uU/mL/405 Standard Deviation 5.2

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Change from baseline in weight, measured in kg.

Outcome measures

Outcome measures
Measure	Losartan Potassium Capsule n=33 Participants Dose will be one 50 mg capsule of losartan per day for one week and then increased to two capsules of 50 mg of losartan per day (100 mg total) for 23 weeks patients with baseline weight ≥ 70 kg to \<150 kg. Losartan potassium: Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype	Placebo Losartan Capsule n=34 Participants Dose will be one 50 mg capsule of placebo losartan per day for one week and then increased to two capsules of 50 mg of placebo losartan per day (100 mg total) for 23 weeks for patients with baseline weight ≥ 70 kg to \<150 kg. Placebo losartan capsule: Matching placebo losartan oral capsule
Change in Weight at 24 Weeks Compared to Baseline	4.4 kg Standard Deviation 4.2	3.9 kg Standard Deviation 4.3

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Change from baseline in BMI, measured in kg/m\^2.

Outcome measures

Outcome measures
Measure	Losartan Potassium Capsule n=33 Participants Dose will be one 50 mg capsule of losartan per day for one week and then increased to two capsules of 50 mg of losartan per day (100 mg total) for 23 weeks patients with baseline weight ≥ 70 kg to \<150 kg. Losartan potassium: Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype	Placebo Losartan Capsule n=34 Participants Dose will be one 50 mg capsule of placebo losartan per day for one week and then increased to two capsules of 50 mg of placebo losartan per day (100 mg total) for 23 weeks for patients with baseline weight ≥ 70 kg to \<150 kg. Placebo losartan capsule: Matching placebo losartan oral capsule
Change in Body Mass Index (BMI) at 24 Weeks Compared to Baseline.	0.8 kg/m^2 Standard Deviation 1.2	0.8 kg/m^2 Standard Deviation 1.3

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Change from baseline in waist circumference, measured in centimeters.

Outcome measures

Outcome measures
Measure	Losartan Potassium Capsule n=33 Participants Dose will be one 50 mg capsule of losartan per day for one week and then increased to two capsules of 50 mg of losartan per day (100 mg total) for 23 weeks patients with baseline weight ≥ 70 kg to \<150 kg. Losartan potassium: Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype	Placebo Losartan Capsule n=34 Participants Dose will be one 50 mg capsule of placebo losartan per day for one week and then increased to two capsules of 50 mg of placebo losartan per day (100 mg total) for 23 weeks for patients with baseline weight ≥ 70 kg to \<150 kg. Placebo losartan capsule: Matching placebo losartan oral capsule
Change in Waist Circumference at 24 Weeks Compared to Baseline	2.6 cm Standard Deviation 5.4	0.1 cm Standard Deviation 6.4

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Change from baseline in waist-to-hip ratio, measured as the circumference of the waist in centimeters divided by the circumference of the hips in centimeters.

Outcome measures

Outcome measures
Measure	Losartan Potassium Capsule n=33 Participants Dose will be one 50 mg capsule of losartan per day for one week and then increased to two capsules of 50 mg of losartan per day (100 mg total) for 23 weeks patients with baseline weight ≥ 70 kg to \<150 kg. Losartan potassium: Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype	Placebo Losartan Capsule n=34 Participants Dose will be one 50 mg capsule of placebo losartan per day for one week and then increased to two capsules of 50 mg of placebo losartan per day (100 mg total) for 23 weeks for patients with baseline weight ≥ 70 kg to \<150 kg. Placebo losartan capsule: Matching placebo losartan oral capsule
Change in Waist-to-hip Ratio at 24 Weeks Compared to Baseline	0.01 ratio Standard Deviation 0.05	-0.01 ratio Standard Deviation 0.06

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Pediatric Quality of Life Inventory (PedsQOL) version 4.0 is composed of 23 items comprising 4 dimensions: Physical Functioning, Emotional Functioning, Social Functioning, and School Functioning. Scores are transformed on a scale from 0 to 100, with higher scores indicating better health-related quality of life. Physical Health Summary Score =Physical Functioning Scale Score. The outcome is 24-week change from baseline in PedsQOL Physical Health Score, where higher values indicate improvement in quality of life.

Outcome measures

Outcome measures
Measure	Losartan Potassium Capsule n=33 Participants Dose will be one 50 mg capsule of losartan per day for one week and then increased to two capsules of 50 mg of losartan per day (100 mg total) for 23 weeks patients with baseline weight ≥ 70 kg to \<150 kg. Losartan potassium: Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype	Placebo Losartan Capsule n=34 Participants Dose will be one 50 mg capsule of placebo losartan per day for one week and then increased to two capsules of 50 mg of placebo losartan per day (100 mg total) for 23 weeks for patients with baseline weight ≥ 70 kg to \<150 kg. Placebo losartan capsule: Matching placebo losartan oral capsule
Change in Pediatric Quality of Life Inventory (PedsQOL) Physical Health Score at 24 Weeks Compared to Baseline	0.9 score on a scale Standard Deviation 14.7	-2.2 score on a scale Standard Deviation 13.3

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Numbers of adverse events reported over 24 weeks.

Outcome measures

Outcome measures
Measure	Losartan Potassium Capsule n=33 Participants Dose will be one 50 mg capsule of losartan per day for one week and then increased to two capsules of 50 mg of losartan per day (100 mg total) for 23 weeks patients with baseline weight ≥ 70 kg to \<150 kg. Losartan potassium: Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype	Placebo Losartan Capsule n=34 Participants Dose will be one 50 mg capsule of placebo losartan per day for one week and then increased to two capsules of 50 mg of placebo losartan per day (100 mg total) for 23 weeks for patients with baseline weight ≥ 70 kg to \<150 kg. Placebo losartan capsule: Matching placebo losartan oral capsule
Frequency of Adverse Events Over 24 Weeks	44 adverse events	55 adverse events

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Change from baseline in total cholesterol, measured in mg/dL

Outcome measures

Outcome measures
Measure	Losartan Potassium Capsule n=33 Participants Dose will be one 50 mg capsule of losartan per day for one week and then increased to two capsules of 50 mg of losartan per day (100 mg total) for 23 weeks patients with baseline weight ≥ 70 kg to \<150 kg. Losartan potassium: Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype	Placebo Losartan Capsule n=34 Participants Dose will be one 50 mg capsule of placebo losartan per day for one week and then increased to two capsules of 50 mg of placebo losartan per day (100 mg total) for 23 weeks for patients with baseline weight ≥ 70 kg to \<150 kg. Placebo losartan capsule: Matching placebo losartan oral capsule
Change in Total Cholesterol at 24 Weeks Compared to Baseline	-6.7 mg/dL Standard Deviation 28.4	-4.1 mg/dL Standard Deviation 25.2

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Change from baseline in triglycerides, measured in mg/dL

Outcome measures

Outcome measures
Measure	Losartan Potassium Capsule n=33 Participants Dose will be one 50 mg capsule of losartan per day for one week and then increased to two capsules of 50 mg of losartan per day (100 mg total) for 23 weeks patients with baseline weight ≥ 70 kg to \<150 kg. Losartan potassium: Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype	Placebo Losartan Capsule n=34 Participants Dose will be one 50 mg capsule of placebo losartan per day for one week and then increased to two capsules of 50 mg of placebo losartan per day (100 mg total) for 23 weeks for patients with baseline weight ≥ 70 kg to \<150 kg. Placebo losartan capsule: Matching placebo losartan oral capsule
Change in Triglycerides at 24 Weeks Compared to Baseline	13.2 mg/dL Standard Deviation 98.1	6.2 mg/dL Standard Deviation 41.1

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Change from baseline in HDL cholesterol, measured in mg/dL

Outcome measures

Outcome measures
Measure	Losartan Potassium Capsule n=33 Participants Dose will be one 50 mg capsule of losartan per day for one week and then increased to two capsules of 50 mg of losartan per day (100 mg total) for 23 weeks patients with baseline weight ≥ 70 kg to \<150 kg. Losartan potassium: Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype	Placebo Losartan Capsule n=34 Participants Dose will be one 50 mg capsule of placebo losartan per day for one week and then increased to two capsules of 50 mg of placebo losartan per day (100 mg total) for 23 weeks for patients with baseline weight ≥ 70 kg to \<150 kg. Placebo losartan capsule: Matching placebo losartan oral capsule
Change in HDL Cholesterol at 24 Weeks Compared to Baseline	-2.1 mg/dL Standard Deviation 6.2	-1.1 mg/dL Standard Deviation 4.9

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Change from baseline in LDL cholesterol, measured in mg/dL

Outcome measures

Outcome measures
Measure	Losartan Potassium Capsule n=33 Participants Dose will be one 50 mg capsule of losartan per day for one week and then increased to two capsules of 50 mg of losartan per day (100 mg total) for 23 weeks patients with baseline weight ≥ 70 kg to \<150 kg. Losartan potassium: Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype	Placebo Losartan Capsule n=34 Participants Dose will be one 50 mg capsule of placebo losartan per day for one week and then increased to two capsules of 50 mg of placebo losartan per day (100 mg total) for 23 weeks for patients with baseline weight ≥ 70 kg to \<150 kg. Placebo losartan capsule: Matching placebo losartan oral capsule
Change in LDL Cholesterol at 24 Weeks Compared to Baseline	-6.7 mg/dL Standard Deviation 29.2	-6.2 mg/dL Standard Deviation 14.8

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Pediatric Quality of Life Inventory (PedsQOL) version 4.0 is composed of 23 items comprising 4 dimensions: Physical Functioning, Emotional Functioning, Social Functioning, and School Functioning. Scores are transformed on a scale from 0 to 100, with higher scores indicating better health-related quality of life. Psychosocial Health Summary Score = Sum of items over the number of items answered in the Emotional, Social, and School Functioning Scales. The outcome is 24-week change from baseline in PedsQOL Psychosocial Health Score, where higher values indicate improvement in quality of life.

Outcome measures

Outcome measures
Measure	Losartan Potassium Capsule n=33 Participants Dose will be one 50 mg capsule of losartan per day for one week and then increased to two capsules of 50 mg of losartan per day (100 mg total) for 23 weeks patients with baseline weight ≥ 70 kg to \<150 kg. Losartan potassium: Losartan potassium is an angiotensin II receptor blocker acting on the AT 1 receptor subtype	Placebo Losartan Capsule n=34 Participants Dose will be one 50 mg capsule of placebo losartan per day for one week and then increased to two capsules of 50 mg of placebo losartan per day (100 mg total) for 23 weeks for patients with baseline weight ≥ 70 kg to \<150 kg. Placebo losartan capsule: Matching placebo losartan oral capsule
Change in Pediatric Quality of Life Inventory (PedsQOL) Psychosocial Health Score at 24 Weeks Compared to Baseline	2.7 score on a scale Standard Deviation 12.2	-0.2 score on a scale Standard Deviation 13.9

Adverse Events

Losartan

Serious events: 0 serious events

Other events: 28 other events

Deaths: 0 deaths

Placebo

Serious events: 4 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Losartan n=43 participants at risk 100 mg losartan once per day	Placebo n=40 participants at risk Matching placebo, taken once per day
Hepatobiliary disorders Cholecystitis	0.00% 0/43 • Adverse event data were collected over a time period of 36 weeks.	2.5% 1/40 • Number of events 1 • Adverse event data were collected over a time period of 36 weeks.
Psychiatric disorders Suicidal ideation	0.00% 0/43 • Adverse event data were collected over a time period of 36 weeks.	2.5% 1/40 • Number of events 1 • Adverse event data were collected over a time period of 36 weeks.
Infections and infestations Wound infection	0.00% 0/43 • Adverse event data were collected over a time period of 36 weeks.	2.5% 1/40 • Number of events 1 • Adverse event data were collected over a time period of 36 weeks.
Surgical and medical procedures Surgical and medication procedures - Other, bilateral knee surgery	0.00% 0/43 • Adverse event data were collected over a time period of 36 weeks.	2.5% 1/40 • Number of events 1 • Adverse event data were collected over a time period of 36 weeks.

Other adverse events

Additional Information

Laura Wilson

Johns Hopkins Bloomberg School of Public Health

Phone: 410-955-0719

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Losartan n=43 participants at risk 100 mg losartan once per day	Placebo n=40 participants at risk Matching placebo, taken once per day
Gastrointestinal disorders Abdominal pain	4.7% 2/43 • Number of events 2 • Adverse event data were collected over a time period of 36 weeks.	2.5% 1/40 • Number of events 1 • Adverse event data were collected over a time period of 36 weeks.
Musculoskeletal and connective tissue disorders Back pain	2.3% 1/43 • Number of events 1 • Adverse event data were collected over a time period of 36 weeks.	2.5% 1/40 • Number of events 1 • Adverse event data were collected over a time period of 36 weeks.
Infections and infestations Conjunctivitis	0.00% 0/43 • Adverse event data were collected over a time period of 36 weeks.	2.5% 1/40 • Number of events 1 • Adverse event data were collected over a time period of 36 weeks.
Respiratory, thoracic and mediastinal disorders Cough	2.3% 1/43 • Number of events 1 • Adverse event data were collected over a time period of 36 weeks.	2.5% 1/40 • Number of events 1 • Adverse event data were collected over a time period of 36 weeks.
Gastrointestinal disorders Diarrhea	4.7% 2/43 • Number of events 2 • Adverse event data were collected over a time period of 36 weeks.	5.0% 2/40 • Number of events 2 • Adverse event data were collected over a time period of 36 weeks.
Nervous system disorders Dizziness	11.6% 5/43 • Number of events 5 • Adverse event data were collected over a time period of 36 weeks.	7.5% 3/40 • Number of events 4 • Adverse event data were collected over a time period of 36 weeks.
Gastrointestinal disorders Dyspepsia	4.7% 2/43 • Number of events 2 • Adverse event data were collected over a time period of 36 weeks.	2.5% 1/40 • Number of events 1 • Adverse event data were collected over a time period of 36 weeks.
Respiratory, thoracic and mediastinal disorders Epistaxis	2.3% 1/43 • Number of events 1 • Adverse event data were collected over a time period of 36 weeks.	0.00% 0/40 • Adverse event data were collected over a time period of 36 weeks.
General disorders Fatigue	2.3% 1/43 • Number of events 1 • Adverse event data were collected over a time period of 36 weeks.	0.00% 0/40 • Adverse event data were collected over a time period of 36 weeks.
General disorders Fever	2.3% 1/43 • Number of events 1 • Adverse event data were collected over a time period of 36 weeks.	2.5% 1/40 • Number of events 1 • Adverse event data were collected over a time period of 36 weeks.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/43 • Adverse event data were collected over a time period of 36 weeks.	2.5% 1/40 • Number of events 1 • Adverse event data were collected over a time period of 36 weeks.
Respiratory, thoracic and mediastinal disorders Flu like symptoms	4.7% 2/43 • Number of events 2 • Adverse event data were collected over a time period of 36 weeks.	0.00% 0/40 • Adverse event data were collected over a time period of 36 weeks.
Nervous system disorders Headache	16.3% 7/43 • Number of events 7 • Adverse event data were collected over a time period of 36 weeks.	17.5% 7/40 • Number of events 7 • Adverse event data were collected over a time period of 36 weeks.
Cardiac disorders Hypertension	0.00% 0/43 • Adverse event data were collected over a time period of 36 weeks.	5.0% 2/40 • Number of events 2 • Adverse event data were collected over a time period of 36 weeks.
Cardiac disorders Hypotension	4.7% 2/43 • Number of events 2 • Adverse event data were collected over a time period of 36 weeks.	0.00% 0/40 • Adverse event data were collected over a time period of 36 weeks.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder, other - knee injury, pain, bursitis	2.3% 1/43 • Number of events 1 • Adverse event data were collected over a time period of 36 weeks.	0.00% 0/40 • Adverse event data were collected over a time period of 36 weeks.
Ear and labyrinth disorders Middle ear inflammation	2.3% 1/43 • Number of events 1 • Adverse event data were collected over a time period of 36 weeks.	0.00% 0/40 • Adverse event data were collected over a time period of 36 weeks.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder, other-slipped capital femoral epiphysis (SCFE)	0.00% 0/43 • Adverse event data were collected over a time period of 36 weeks.	2.5% 1/40 • Number of events 1 • Adverse event data were collected over a time period of 36 weeks.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/43 • Adverse event data were collected over a time period of 36 weeks.	2.5% 1/40 • Number of events 1 • Adverse event data were collected over a time period of 36 weeks.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/43 • Adverse event data were collected over a time period of 36 weeks.	2.5% 1/40 • Number of events 1 • Adverse event data were collected over a time period of 36 weeks.
Gastrointestinal disorders Nausea	7.0% 3/43 • Number of events 3 • Adverse event data were collected over a time period of 36 weeks.	12.5% 5/40 • Number of events 5 • Adverse event data were collected over a time period of 36 weeks.
Ear and labyrinth disorders Otitis externa	0.00% 0/43 • Adverse event data were collected over a time period of 36 weeks.	2.5% 1/40 • Number of events 1 • Adverse event data were collected over a time period of 36 weeks.
Respiratory, thoracic and mediastinal disorders Pharyngitis	0.00% 0/43 • Adverse event data were collected over a time period of 36 weeks.	2.5% 1/40 • Number of events 1 • Adverse event data were collected over a time period of 36 weeks.
Surgical and medical procedures Surgical and medical procedures - Other, Rhinoseptoplasty	2.3% 1/43 • Number of events 1 • Adverse event data were collected over a time period of 36 weeks.	0.00% 0/40 • Adverse event data were collected over a time period of 36 weeks.
Infections and infestations Rash, pustular	0.00% 0/43 • Adverse event data were collected over a time period of 36 weeks.	2.5% 1/40 • Number of events 1 • Adverse event data were collected over a time period of 36 weeks.
Respiratory, thoracic and mediastinal disorders Rhinorrhea	0.00% 0/43 • Adverse event data were collected over a time period of 36 weeks.	2.5% 1/40 • Number of events 1 • Adverse event data were collected over a time period of 36 weeks.
Infections and infestations Sinusitus	4.7% 2/43 • Number of events 2 • Adverse event data were collected over a time period of 36 weeks.	2.5% 1/40 • Number of events 1 • Adverse event data were collected over a time period of 36 weeks.
Infections and infestations Sore throat	2.3% 1/43 • Number of events 1 • Adverse event data were collected over a time period of 36 weeks.	2.5% 1/40 • Number of events 1 • Adverse event data were collected over a time period of 36 weeks.
Gastrointestinal disorders Stomach pain	4.7% 2/43 • Number of events 2 • Adverse event data were collected over a time period of 36 weeks.	2.5% 1/40 • Number of events 1 • Adverse event data were collected over a time period of 36 weeks.
Respiratory, thoracic and mediastinal disorders Upper respiratory infection	4.7% 2/43 • Number of events 2 • Adverse event data were collected over a time period of 36 weeks.	17.5% 7/40 • Number of events 9 • Adverse event data were collected over a time period of 36 weeks.
Infections and infestations Viremia	0.00% 0/43 • Adverse event data were collected over a time period of 36 weeks.	2.5% 1/40 • Number of events 1 • Adverse event data were collected over a time period of 36 weeks.
Gastrointestinal disorders Vomiting	2.3% 1/43 • Number of events 1 • Adverse event data were collected over a time period of 36 weeks.	2.5% 1/40 • Number of events 1 • Adverse event data were collected over a time period of 36 weeks.
Gastrointestinal disorders Flatulence	2.3% 1/43 • Number of events 1 • Adverse event data were collected over a time period of 36 weeks.	0.00% 0/40 • Adverse event data were collected over a time period of 36 weeks.