Trial Outcomes & Findings for Natrecor (Nesiritide) in Transplant-Eligible Management of Congestive Heart Failure-TMAC (NCT NCT00338455)

Last Updated: 2014-12-08

Results Overview

Number of calendar days alive without renal, hemodynamic, or electrical clinical worsening through Day 28 (termination of treatment or early discontinuation of treatment, whichever occurred first). The endpoint was not normalized for time on study.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

16 participants

Primary outcome timeframe

28 days

Results posted on

2014-12-08

Participant Flow

Of the 16 participants randomized in the study, 1 participant randomized to receive nesiritide was not administered study drug due to investigator decision.Summaries of baseline characteristics are based on the 16 participants who were randomized in the study. Safety and efficacy analyses were based on the 15 participantswho received study drug.

Participant milestones

Participant milestones
Measure	Natrecor (Nesiritide)+Standard Care+Dobutamine or Milrinone Nesiritide - 28-day continuous infusion, no bolus; 3-hour 0.005 mcg/kg/min, may be titrated to 0.015 mcg/kg/min.	Placebo + Standard Care + Dobutamine or Milrinone Placebo - 28-day continuous infusion, no bolus; 3-hour 0.005 mcg/kg/min, may be titrated to 0.015 mcg/kg/min.
Overall Study STARTED	9	7
Overall Study Administered Study Drug	8	7
Overall Study COMPLETED	6	6
Overall Study NOT COMPLETED	3	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Natrecor (Nesiritide)+Standard Care+Dobutamine or Milrinone Nesiritide - 28-day continuous infusion, no bolus; 3-hour 0.005 mcg/kg/min, may be titrated to 0.015 mcg/kg/min.	Placebo + Standard Care + Dobutamine or Milrinone Placebo - 28-day continuous infusion, no bolus; 3-hour 0.005 mcg/kg/min, may be titrated to 0.015 mcg/kg/min.
Overall Study Death	2	1
Overall Study Physician Decision	1	0

Baseline Characteristics

Natrecor (Nesiritide) in Transplant-Eligible Management of Congestive Heart Failure-TMAC

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Natrecor (Nesiritide)+Standard Care+Dobutamine or Milrinone n=9 Participants Nesiritide - 28-day continuous infusion, no bolus; 3-hour 0.005 mcg/kg/min, may be titrated to 0.015 mcg/kg/min.	Placebo + Standard Care + Dobutamine or Milrinone n=7 Participants Placebo - 28-day continuous infusion, no bolus; 3-hour 0.005 mcg/kg/min, may be titrated to 0.015 mcg/kg/min.	Total n=16 Participants Total of all reporting groups
Age, Continuous	52.0 years STANDARD_DEVIATION 9.80 • n=5 Participants	54.6 years STANDARD_DEVIATION 4.65 • n=7 Participants	53.1 years STANDARD_DEVIATION 7.85 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	4 Participants n=7 Participants	12 Participants n=5 Participants
Glomerular Filtration Rate (GFR) GFR < 60	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Glomerular Filtration Rate (GFR) GFR > = 60	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Body Mass Index (BMI)	29.4 kg/m^2 STANDARD_DEVIATION 5.53 • n=5 Participants	31.7 kg/m^2 STANDARD_DEVIATION 5.79 • n=7 Participants	30.5 kg/m^2 STANDARD_DEVIATION 5.57 • n=5 Participants

PRIMARY outcome

Timeframe: 28 days

Population: Early termination of the study due to enrollment difficulties; efficacy not analyzed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 28 days

Population: Early termination of the study due to enrollment difficulties; efficacy not analyzed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 30 and Months 2 and 6

Population: Early termination of the study due to enrollment difficulties; efficacy not analyzed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 28 days

Population: Early termination of the study due to enrollment difficulties; efficacy not analyzed.

Outcome measures

Outcome data not reported

Adverse Events

Natrecor (Nesiritide)+Standard Care+Dobutamine or Milrinone

Serious events: 4 serious events

Other events: 7 other events

Deaths: 0 deaths

Placebo + Standard Care + Dobutamine or Milrinone

Serious events: 3 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Natrecor (Nesiritide)+Standard Care+Dobutamine or Milrinone n=8 participants at risk Nesiritide - 28-day continuous infusion, no bolus; 3-hour 0.005 mcg/kg/min, may be titrated to 0.015 mcg/kg/min.	Placebo + Standard Care + Dobutamine or Milrinone n=7 participants at risk Placebo - 28-day continuous infusion, no bolus; 3-hour 0.005 mcg/kg/min, may be titrated to 0.015 mcg/kg/min.
Infections and infestations sepsis	12.5% 1/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	0.00% 0/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
Respiratory, thoracic and mediastinal disorders pneumothorax	12.5% 1/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	0.00% 0/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
Infections and infestations pneumonia	12.5% 1/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	0.00% 0/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
Respiratory, thoracic and mediastinal disorders cardiac failure congestive	37.5% 3/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	14.3% 1/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
Cardiac disorders cardiac failure	0.00% 0/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	14.3% 1/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
Infections and infestations gastroenteritis	12.5% 1/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	0.00% 0/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
Respiratory, thoracic and mediastinal disorders dyspnoea	12.5% 1/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	0.00% 0/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
Metabolism and nutrition disorders hypovolaemia	0.00% 0/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	14.3% 1/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
Immune system disorders anaphylactic reaction	0.00% 0/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	14.3% 1/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
Nervous system disorders convulsion	0.00% 0/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	14.3% 1/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
Infections and infestations staphylococcal sepsis	0.00% 0/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	14.3% 1/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.

Other adverse events

Additional Information

Sr. Director Clinical Leader

Scios R&D, Inc.

Phone: 650 564-5084

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Natrecor (Nesiritide)+Standard Care+Dobutamine or Milrinone n=8 participants at risk Nesiritide - 28-day continuous infusion, no bolus; 3-hour 0.005 mcg/kg/min, may be titrated to 0.015 mcg/kg/min.	Placebo + Standard Care + Dobutamine or Milrinone n=7 participants at risk Placebo - 28-day continuous infusion, no bolus; 3-hour 0.005 mcg/kg/min, may be titrated to 0.015 mcg/kg/min.
Metabolism and nutrition disorders gout	25.0% 2/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	0.00% 0/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
Gastrointestinal disorders nausea	25.0% 2/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	14.3% 1/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
Gastrointestinal disorders constipation	12.5% 1/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	14.3% 1/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
Respiratory, thoracic and mediastinal disorders dyspnoea	0.00% 0/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	14.3% 1/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
Respiratory, thoracic and mediastinal disorders pharyngolaryngeal pain	12.5% 1/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	14.3% 1/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
General disorders oedema peripheral	12.5% 1/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	14.3% 1/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
Vascular disorders hypotension	12.5% 1/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	14.3% 1/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
Infections and infestations catheter site infection	12.5% 1/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	0.00% 0/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
Infections and infestations clostridial infection	12.5% 1/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	0.00% 0/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
Infections and infestations clostridium colitis	12.5% 1/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	0.00% 0/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
Infections and infestations naospharyngitis	0.00% 0/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	14.3% 1/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
Infections and infestations staphylococcal infection	0.00% 0/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	14.3% 1/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
Infections and infestations urinary tract infection	0.00% 0/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	14.3% 1/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
General disorders catheter related complication	12.5% 1/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	0.00% 0/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
General disorders catheter site discharge	12.5% 1/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	0.00% 0/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
Respiratory, thoracic and mediastinal disorders rales	0.00% 0/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	14.3% 1/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
Skin and subcutaneous tissue disorders dry skin	12.5% 1/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	0.00% 0/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
Skin and subcutaneous tissue disorders ecchymosis	0.00% 0/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	14.3% 1/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
Skin and subcutaneous tissue disorders erythema	0.00% 0/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	14.3% 1/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
Vascular disorders deep vein thrombosis	12.5% 1/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	0.00% 0/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
Vascular disorders jugular vein distension	0.00% 0/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	14.3% 1/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
Investigations blood creatinine increased	12.5% 1/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	0.00% 0/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
Investigations blood glucose increased	0.00% 0/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	14.3% 1/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
Investigations gallop rythm present	12.5% 1/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	0.00% 0/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
Hepatobiliary disorders hepatomegaly	0.00% 0/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	14.3% 1/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
Metabolism and nutrition disorders dehydration	12.5% 1/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	0.00% 0/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
Metabolism and nutrition disorders hypervolaemia	0.00% 0/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	14.3% 1/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
Metabolism and nutrition disorders hypochloraemia	0.00% 0/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	14.3% 1/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
Metabolism and nutrition disorders hypokalaemia	12.5% 1/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	0.00% 0/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
Metabolism and nutrition disorders hyponatraemia	0.00% 0/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	14.3% 1/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
Gastrointestinal disorders dyspepsia	0.00% 0/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	14.3% 1/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
Injury, poisoning and procedural complications post procedural haemorrhage	12.5% 1/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	0.00% 0/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
Psychiatric disorders depression	12.5% 1/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	0.00% 0/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.
Psychiatric disorders insomnia	12.5% 1/8 • Safety evaluations were to be performed on treatment and at Months 2 and 6.	0.00% 0/7 • Safety evaluations were to be performed on treatment and at Months 2 and 6.