Trial Outcomes & Findings for Study of Dopamine Versus Vasopressin for Treatment of Low Blood Pressure in Low Birth Weight Infants (NCT NCT01318278)

NCT ID: NCT01318278

Last Updated: 2019-02-20

Results Overview

Optimal mean blood pressure (OMBP) will be defined as either a 10% increase in mean blood pressure value or a 2-3 mmHg rise in mean blood pressure value AND an improvement in tissue perfusion as demonstrated by a resolution in the specified clinical symptom (designated upon enrollment) within 4-6 hours of having reached OMBP

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 70 participants
• Primary outcome timeframe: 24 hours of life
• Results posted on: 2019-02-20

Participant Flow

Participant milestones

Measure	Dopamine Treatment Dopamine treatment beginning at 5 mcg/kg/min and titrated by 5 mcg/kg/min to effect up to maximum of 20 mcg/kg/min Dopamine: dopamine at low/medium/and high dose (5, 10, 15, and 20 mcg/kg/min) given IV as a continuous infusion, titrated up for efficacy	Vasopressin Treatment Arginine Vasopressin treatment beginning at 0.01 units/kg/hr and titrated up by 0.01 units/kg/hr to effect up to a maximum of 0.04 units/kg/hr Arginine Vasopressin: vasopressin at low/medium/and high dose (0.01, 0.02, 0.03, or 0.04 units/kg/hr) given IV as a continuous infusion, titrated up for efficacy	Comparison Arm Infants who did not require vasopressor support for hypotension during the first 24 hours of life
Overall Study STARTED	10	10	50
Overall Study COMPLETED	10	10	50
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of Dopamine Versus Vasopressin for Treatment of Low Blood Pressure in Low Birth Weight Infants

Baseline characteristics by cohort

Measure	Dopamine Treatment n=10 Participants Dopamine treatment beginning at 5 mcg/kg/min and titrated by 5 mcg/kg/min to effect up to maximum of 20 mcg/kg/min Dopamine: dopamine at low/medium/and high dose (5, 10, 15, and 20 mcg/kg/min) given IV as a continuous infusion, titrated up for efficacy	Vasopressin Treatment n=10 Participants Arginine Vasopressin treatment beginning at 0.01 units/kg/hr and titrated up by 0.01 units/kg/hr to effect up to a maximum of 0.04 units/kg/hr Arginine Vasopressin: vasopressin at low/medium/and high dose (0.01, 0.02, 0.03, or 0.04 units/kg/hr) given IV as a continuous infusion, titrated up for efficacy	Comparison Arm n=50 Participants Infants who did not require vasopressor support for hypotension during the first 24 hours of life	Total n=70 Participants Total of all reporting groups
Age, Continuous	25.1 weeks STANDARD_DEVIATION 1 • n=5 Participants	25.7 weeks STANDARD_DEVIATION 2 • n=7 Participants	25.6 weeks STANDARD_DEVIATION 1 • n=5 Participants	25.6 weeks STANDARD_DEVIATION 1.4 • n=4 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	4 Participants n=7 Participants	28 Participants n=5 Participants	37 Participants n=4 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	6 Participants n=7 Participants	22 Participants n=5 Participants	33 Participants n=4 Participants

PRIMARY outcome

Timeframe: 24 hours of life

Population: This outcome is only reportable in the two treatment groups as it evaluates the response to treatment of hypotension in those who received study drug. The comparison group infants were not hypotensive within the 24 hours and did not receive study drug, therefore, they are omitted from this outcome measure.

Optimal mean blood pressure (OMBP) will be defined as either a 10% increase in mean blood pressure value or a 2-3 mmHg rise in mean blood pressure value AND an improvement in tissue perfusion as demonstrated by a resolution in the specified clinical symptom (designated upon enrollment) within 4-6 hours of having reached OMBP

Outcome measures

Measure	Dopamine Treatment n=10 Participants Dopamine treatment beginning at 5 mcg/kg/min and titrated by 5 mcg/kg/min to effect up to maximum of 20 mcg/kg/min Dopamine: dopamine at low/medium/and high dose (5, 10, 15, and 20 mcg/kg/min) given IV as a continuous infusion, titrated up for efficacy	Vasopressin Treatment n=10 Participants Arginine Vasopressin treatment beginning at 0.01 units/kg/hr and titrated up by 0.01 units/kg/hr to effect up to a maximum of 0.04 units/kg/hr Arginine Vasopressin: vasopressin at low/medium/and high dose (0.01, 0.02, 0.03, or 0.04 units/kg/hr) given IV as a continuous infusion, titrated up for efficacy	Comparison Group Infants not diagnosed with hypotension in first 24 hours
Number of Subjects in Each Group Who Have Achieved an Optimal Mean Blood Pressure Value at 24 Hours of Life	9 participants	9 participants	—

SECONDARY outcome

Timeframe: 96 hours or until hypotension completely resolved and medications stopped

Population: This outcome is only reportable in the two treatment groups as it evaluates the change in heart rate in those who received study drug. The comparison group infants were not hypotensive within the 24 hours and did not receive study drug, therefore, they are omitted from this outcome measure.

Heart rate change from baseline during study drug administration

Outcome measures

Measure	Dopamine Treatment n=10 Participants Dopamine treatment beginning at 5 mcg/kg/min and titrated by 5 mcg/kg/min to effect up to maximum of 20 mcg/kg/min Dopamine: dopamine at low/medium/and high dose (5, 10, 15, and 20 mcg/kg/min) given IV as a continuous infusion, titrated up for efficacy	Vasopressin Treatment n=10 Participants Arginine Vasopressin treatment beginning at 0.01 units/kg/hr and titrated up by 0.01 units/kg/hr to effect up to a maximum of 0.04 units/kg/hr Arginine Vasopressin: vasopressin at low/medium/and high dose (0.01, 0.02, 0.03, or 0.04 units/kg/hr) given IV as a continuous infusion, titrated up for efficacy	Comparison Group Infants not diagnosed with hypotension in first 24 hours
Heart Rate Change From Baseline	31 beats per minute Standard Deviation 19	0 beats per minute Standard Deviation 10	—

SECONDARY outcome

Timeframe: 96 hours or until hypotension resolved and medication completely stopped

Population: Treatment groups during study drug administration. Comparison group during first 96 hours of life. For all- only arterial gases

Outcome measures

Measure	Dopamine Treatment n=10 Participants Dopamine treatment beginning at 5 mcg/kg/min and titrated by 5 mcg/kg/min to effect up to maximum of 20 mcg/kg/min Dopamine: dopamine at low/medium/and high dose (5, 10, 15, and 20 mcg/kg/min) given IV as a continuous infusion, titrated up for efficacy	Vasopressin Treatment n=10 Participants Arginine Vasopressin treatment beginning at 0.01 units/kg/hr and titrated up by 0.01 units/kg/hr to effect up to a maximum of 0.04 units/kg/hr Arginine Vasopressin: vasopressin at low/medium/and high dose (0.01, 0.02, 0.03, or 0.04 units/kg/hr) given IV as a continuous infusion, titrated up for efficacy	Comparison Group n=50 Participants Infants not diagnosed with hypotension in first 24 hours
Acid-base Status	7.18 pH Standard Deviation .07	7.2 pH Standard Deviation .07	7.25 pH Standard Deviation .09

SECONDARY outcome

Timeframe: 96 hours or until medication completely stopped

Outcome measures

Measure	Dopamine Treatment n=10 Participants Dopamine treatment beginning at 5 mcg/kg/min and titrated by 5 mcg/kg/min to effect up to maximum of 20 mcg/kg/min Dopamine: dopamine at low/medium/and high dose (5, 10, 15, and 20 mcg/kg/min) given IV as a continuous infusion, titrated up for efficacy	Vasopressin Treatment n=10 Participants Arginine Vasopressin treatment beginning at 0.01 units/kg/hr and titrated up by 0.01 units/kg/hr to effect up to a maximum of 0.04 units/kg/hr Arginine Vasopressin: vasopressin at low/medium/and high dose (0.01, 0.02, 0.03, or 0.04 units/kg/hr) given IV as a continuous infusion, titrated up for efficacy	Comparison Group n=50 Participants Infants not diagnosed with hypotension in first 24 hours
Hyponatremia	3 participants	3 participants	11 participants

SECONDARY outcome

Timeframe: 96 hours or until hypotension resolved and medication completely stopped

Outcome measures

Measure	Dopamine Treatment n=10 Participants Dopamine treatment beginning at 5 mcg/kg/min and titrated by 5 mcg/kg/min to effect up to maximum of 20 mcg/kg/min Dopamine: dopamine at low/medium/and high dose (5, 10, 15, and 20 mcg/kg/min) given IV as a continuous infusion, titrated up for efficacy	Vasopressin Treatment n=10 Participants Arginine Vasopressin treatment beginning at 0.01 units/kg/hr and titrated up by 0.01 units/kg/hr to effect up to a maximum of 0.04 units/kg/hr Arginine Vasopressin: vasopressin at low/medium/and high dose (0.01, 0.02, 0.03, or 0.04 units/kg/hr) given IV as a continuous infusion, titrated up for efficacy	Comparison Group n=50 Participants Infants not diagnosed with hypotension in first 24 hours
Urine Output	4.4 ml/kg/hr Standard Deviation 1.4	3.5 ml/kg/hr Standard Deviation 1.4	3.9 ml/kg/hr Standard Deviation 1.4

SECONDARY outcome

Timeframe: 96 hours or until medication completely stopped

Physical examinations were done on at least a twice daily basis to evaluate for any ischemic lesions (especially on the limbs) of all subjects. The presence of any lesion considered to be due to ischemia would have been reported in this data.

Outcome measures

Measure	Dopamine Treatment n=10 Participants Dopamine treatment beginning at 5 mcg/kg/min and titrated by 5 mcg/kg/min to effect up to maximum of 20 mcg/kg/min Dopamine: dopamine at low/medium/and high dose (5, 10, 15, and 20 mcg/kg/min) given IV as a continuous infusion, titrated up for efficacy	Vasopressin Treatment n=10 Participants Arginine Vasopressin treatment beginning at 0.01 units/kg/hr and titrated up by 0.01 units/kg/hr to effect up to a maximum of 0.04 units/kg/hr Arginine Vasopressin: vasopressin at low/medium/and high dose (0.01, 0.02, 0.03, or 0.04 units/kg/hr) given IV as a continuous infusion, titrated up for efficacy	Comparison Group n=50 Participants Infants not diagnosed with hypotension in first 24 hours
Evidence of Ischemic Changes	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: until hospital discharge, up to 12 weeks

Outcome measures

Measure	Dopamine Treatment n=10 Participants Dopamine treatment beginning at 5 mcg/kg/min and titrated by 5 mcg/kg/min to effect up to maximum of 20 mcg/kg/min Dopamine: dopamine at low/medium/and high dose (5, 10, 15, and 20 mcg/kg/min) given IV as a continuous infusion, titrated up for efficacy	Vasopressin Treatment n=10 Participants Arginine Vasopressin treatment beginning at 0.01 units/kg/hr and titrated up by 0.01 units/kg/hr to effect up to a maximum of 0.04 units/kg/hr Arginine Vasopressin: vasopressin at low/medium/and high dose (0.01, 0.02, 0.03, or 0.04 units/kg/hr) given IV as a continuous infusion, titrated up for efficacy	Comparison Group n=50 Participants Infants not diagnosed with hypotension in first 24 hours
Necrotizing Enterocolitis	0 participants	1 participants	2 participants

SECONDARY outcome

Timeframe: Until hospital discharge, up to 15 months

Outcome measures

Measure	Dopamine Treatment n=10 Participants Dopamine treatment beginning at 5 mcg/kg/min and titrated by 5 mcg/kg/min to effect up to maximum of 20 mcg/kg/min Dopamine: dopamine at low/medium/and high dose (5, 10, 15, and 20 mcg/kg/min) given IV as a continuous infusion, titrated up for efficacy	Vasopressin Treatment n=10 Participants Arginine Vasopressin treatment beginning at 0.01 units/kg/hr and titrated up by 0.01 units/kg/hr to effect up to a maximum of 0.04 units/kg/hr Arginine Vasopressin: vasopressin at low/medium/and high dose (0.01, 0.02, 0.03, or 0.04 units/kg/hr) given IV as a continuous infusion, titrated up for efficacy	Comparison Group n=50 Participants Infants not diagnosed with hypotension in first 24 hours
Ventilator Days	52 days Interval 37.0 to 160.0	45.5 days Interval 23.5 to 56.0	17.5 days Interval 1.0 to 38.0

SECONDARY outcome

Timeframe: until hospital discharge, up to 12 weeks

Outcome measures

Measure	Dopamine Treatment n=10 Participants Dopamine treatment beginning at 5 mcg/kg/min and titrated by 5 mcg/kg/min to effect up to maximum of 20 mcg/kg/min Dopamine: dopamine at low/medium/and high dose (5, 10, 15, and 20 mcg/kg/min) given IV as a continuous infusion, titrated up for efficacy	Vasopressin Treatment n=10 Participants Arginine Vasopressin treatment beginning at 0.01 units/kg/hr and titrated up by 0.01 units/kg/hr to effect up to a maximum of 0.04 units/kg/hr Arginine Vasopressin: vasopressin at low/medium/and high dose (0.01, 0.02, 0.03, or 0.04 units/kg/hr) given IV as a continuous infusion, titrated up for efficacy	Comparison Group n=50 Participants Infants not diagnosed with hypotension in first 24 hours
Presence of Patent Ductus Arteriosus (PDA)	5 participants	6 participants	34 participants

SECONDARY outcome

Timeframe: Until hospital discharge, up to 15 months

Outcome measures

Measure	Dopamine Treatment n=10 Participants Dopamine treatment beginning at 5 mcg/kg/min and titrated by 5 mcg/kg/min to effect up to maximum of 20 mcg/kg/min Dopamine: dopamine at low/medium/and high dose (5, 10, 15, and 20 mcg/kg/min) given IV as a continuous infusion, titrated up for efficacy	Vasopressin Treatment n=10 Participants Arginine Vasopressin treatment beginning at 0.01 units/kg/hr and titrated up by 0.01 units/kg/hr to effect up to a maximum of 0.04 units/kg/hr Arginine Vasopressin: vasopressin at low/medium/and high dose (0.01, 0.02, 0.03, or 0.04 units/kg/hr) given IV as a continuous infusion, titrated up for efficacy	Comparison Group n=50 Participants Infants not diagnosed with hypotension in first 24 hours
Grade 3 Intraventricular Hemorrhage or Worse on Head Ultrasound	3 participants	3 participants	6 participants

SECONDARY outcome

Timeframe: Until hospital discharge, up to 15 months

All subjects were followed by an ophthalmologist with initial exam at 4-6 weeks of age. The Stages describe the ophthalmoscopic findings at the junction between the vascularized and avascular retina. Each subject is followed until cleared by ophthalmology. For this outcome measure, the most severe stage of disease was used in analysis.

Stage 1 is a faint demarcation line. Stage 2 is an elevated ridge. Stage 3 is extraretinal fibrovascular proliferation (neovascularization). Stage 4 is sub-total retinal detachment. Stage 5 is total retinal detachment. Stages 1 and 2 do not lead to blindness. However, they can progress to the more severe stages.

Outcome measures

Measure	Dopamine Treatment n=10 Participants Dopamine treatment beginning at 5 mcg/kg/min and titrated by 5 mcg/kg/min to effect up to maximum of 20 mcg/kg/min Dopamine: dopamine at low/medium/and high dose (5, 10, 15, and 20 mcg/kg/min) given IV as a continuous infusion, titrated up for efficacy	Vasopressin Treatment n=10 Participants Arginine Vasopressin treatment beginning at 0.01 units/kg/hr and titrated up by 0.01 units/kg/hr to effect up to a maximum of 0.04 units/kg/hr Arginine Vasopressin: vasopressin at low/medium/and high dose (0.01, 0.02, 0.03, or 0.04 units/kg/hr) given IV as a continuous infusion, titrated up for efficacy	Comparison Group n=50 Participants Infants not diagnosed with hypotension in first 24 hours
Retinopathy of Prematurity Stage 3 or Higher	3 participants	2 participants	4 participants

SECONDARY outcome

Timeframe: 36 weeks postmenstrual age

Infants were evaluated for oxygen need at 36 weeks postmenstrual age. If they required supplemental oxygen, they were diagnosed with BPD

Outcome measures

Measure	Dopamine Treatment n=10 Participants Dopamine treatment beginning at 5 mcg/kg/min and titrated by 5 mcg/kg/min to effect up to maximum of 20 mcg/kg/min Dopamine: dopamine at low/medium/and high dose (5, 10, 15, and 20 mcg/kg/min) given IV as a continuous infusion, titrated up for efficacy	Vasopressin Treatment n=10 Participants Arginine Vasopressin treatment beginning at 0.01 units/kg/hr and titrated up by 0.01 units/kg/hr to effect up to a maximum of 0.04 units/kg/hr Arginine Vasopressin: vasopressin at low/medium/and high dose (0.01, 0.02, 0.03, or 0.04 units/kg/hr) given IV as a continuous infusion, titrated up for efficacy	Comparison Group n=50 Participants Infants not diagnosed with hypotension in first 24 hours
Presence of Bronchopulmonary Dysplasia (BPD)	8 participants	4 participants	31 participants

SECONDARY outcome

Timeframe: admission to hospital discharge, up to 15 months

Outcome measures

Measure	Dopamine Treatment n=10 Participants Dopamine treatment beginning at 5 mcg/kg/min and titrated by 5 mcg/kg/min to effect up to maximum of 20 mcg/kg/min Dopamine: dopamine at low/medium/and high dose (5, 10, 15, and 20 mcg/kg/min) given IV as a continuous infusion, titrated up for efficacy	Vasopressin Treatment n=10 Participants Arginine Vasopressin treatment beginning at 0.01 units/kg/hr and titrated up by 0.01 units/kg/hr to effect up to a maximum of 0.04 units/kg/hr Arginine Vasopressin: vasopressin at low/medium/and high dose (0.01, 0.02, 0.03, or 0.04 units/kg/hr) given IV as a continuous infusion, titrated up for efficacy	Comparison Group n=50 Participants Infants not diagnosed with hypotension in first 24 hours
All Cause Mortality	2 participants	4 participants	10 participants

Adverse Events

Dopamine Treatment

Serious events: 8 serious events

Other events: 3 other events

Deaths: 2 deaths

Vasopressin Treatment

Serious events: 7 serious events

Other events: 4 other events

Deaths: 4 deaths

Comparison Arm

Serious events: 22 serious events

Other events: 11 other events

Deaths: 10 deaths

Serious adverse events

Measure	Dopamine Treatment n=10 participants at risk Dopamine treatment beginning at 5 mcg/kg/min and titrated by 5 mcg/kg/min to effect up to maximum of 20 mcg/kg/min Dopamine: dopamine at low/medium/and high dose (5, 10, 15, and 20 mcg/kg/min) given IV as a continuous infusion, titrated up for efficacy	Vasopressin Treatment n=10 participants at risk Arginine Vasopressin treatment beginning at 0.01 units/kg/hr and titrated up by 0.01 units/kg/hr to effect up to a maximum of 0.04 units/kg/hr Arginine Vasopressin: vasopressin at low/medium/and high dose (0.01, 0.02, 0.03, or 0.04 units/kg/hr) given IV as a continuous infusion, titrated up for efficacy	Comparison Arm n=50 participants at risk Infants who did not require vasopressor support for hypotension during the first 24 hours of life
Gastrointestinal disorders Necrotizing Enterocolitis	10.0% 1/10 • Participants were followed for the duration of hospital stay, up to 15 months	0.00% 0/10 • Participants were followed for the duration of hospital stay, up to 15 months	14.0% 7/50 • Participants were followed for the duration of hospital stay, up to 15 months
Gastrointestinal disorders Bowel Perforation	30.0% 3/10 • Participants were followed for the duration of hospital stay, up to 15 months	20.0% 2/10 • Participants were followed for the duration of hospital stay, up to 15 months	8.0% 4/50 • Participants were followed for the duration of hospital stay, up to 15 months
Infections and infestations Sepsis	40.0% 4/10 • Participants were followed for the duration of hospital stay, up to 15 months	50.0% 5/10 • Participants were followed for the duration of hospital stay, up to 15 months	22.0% 11/50 • Participants were followed for the duration of hospital stay, up to 15 months

Other adverse events

Measure	Dopamine Treatment n=10 participants at risk Dopamine treatment beginning at 5 mcg/kg/min and titrated by 5 mcg/kg/min to effect up to maximum of 20 mcg/kg/min Dopamine: dopamine at low/medium/and high dose (5, 10, 15, and 20 mcg/kg/min) given IV as a continuous infusion, titrated up for efficacy	Vasopressin Treatment n=10 participants at risk Arginine Vasopressin treatment beginning at 0.01 units/kg/hr and titrated up by 0.01 units/kg/hr to effect up to a maximum of 0.04 units/kg/hr Arginine Vasopressin: vasopressin at low/medium/and high dose (0.01, 0.02, 0.03, or 0.04 units/kg/hr) given IV as a continuous infusion, titrated up for efficacy	Comparison Arm n=50 participants at risk Infants who did not require vasopressor support for hypotension during the first 24 hours of life
Renal and urinary disorders Hyponatremia	30.0% 3/10 • Participants were followed for the duration of hospital stay, up to 15 months	40.0% 4/10 • Participants were followed for the duration of hospital stay, up to 15 months	22.0% 11/50 • Participants were followed for the duration of hospital stay, up to 15 months

Additional Information

Dr. Danielle R. Rios

Baylor College of Medicine

Phone: 832-826-1380

Email: drrios@texaschildrens.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place