Short-Term Outcome of N-Carbamylglutamate in the Treatment of Acute Hyperammonemia
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|ClinicalTrials.gov Identifier: NCT01599286|
Recruitment Status : Active, not recruiting
First Posted : May 16, 2012
Last Update Posted : May 9, 2019
The overall objective of this drug trial is to determine whether the treatment of acute hyperammonemia with N-carbamyl-L-glutamate (NCG, Carglumic acid) in propionic acidemia (PA), methylmalonic acidemia (MMA), late-onset CPS1 deficiency (CPSD) and late-onset Ornithine transcarbamylase deficiency (OTCD) accelerates the resolution of hyperammonemia efficiently and safely.
The primary goal is to determine if the study drug (NCG) efficiently reduces ammonia levels following a hyperammonemia episode(s).
Secondly, the investigators want to know if treatment with this study drug (NCG) efficiently improves neurologic function, reduces plasma glutamine levels and lessens the duration of hospitalization after each episode of hyperammonemia.
|Condition or disease||Intervention/treatment||Phase|
|Propionic Acidemia, Type I and/or Type II Methylmalonic Acidemia Carbamoyl-Phosphate Synthase I Deficiency Disease Ornithine Carbamoyltransferase Deficiency||Drug: Carbaglu Drug: Placebo Drug: Standard of Care Treatment||Phase 2|
This is a double-blind, placebo-controlled, randomized clinical drug trial to evaluate the efficacy of NCG in the treatment of two organic acidemias (severe PA and MMA), and two urea-cycle disorders (late-onset CPSD and OTCD).
Primarily, the investigators want to determine whether NCG treatment of acute hyperammonemia in severe, neonatal-onset PA, MMA, CPSD, and OTCD is efficacious and whether it is safe. The investigators will approach this task in two ways.
Assess Whether NCG Treatment is Effective
The objective of this study is to assess whether NCG is efficacious in treating hyperammonemia and improving outcome:
The investigators will realize this goal by randomizing each hyperammonemic episode from every subject to NCG (NCG)+standard treatment (NCG-STD) versus placebo+standard treatment (PLBO-STD) and subsequently gauging response with the primary outcome of plasma ammonia levels, in addition to the plasma glutamine, the Functional Status Scale, and the length of hospitalization.
The primary safety outcome of the study will be the assessed via the rate of Serious Adverse Events (SAEs), defined in this study as death or substantial prolongation of hospitalization, as patients are hospitalized as part of the entry to the study.
Safety tests consisting of complete blood count (CBC), liver and kidney function tests, and coagulation profile (PTT/INR) will be performed before treatment, between days 3-5 of treatment, and just prior to discontinuation of NCG. An electrocardiogram will be performed before treatment and on the third day of treatment or before discharge if earlier.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||114 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Short-Term Outcome of N-Carbamylglutamate in the Treatment of Acute Hyperammonemia|
|Actual Study Start Date :||September 2012|
|Estimated Primary Completion Date :||April 30, 2019|
|Estimated Study Completion Date :||April 30, 2020|
Experimental: Active Comparator
Parallel Trial Comparing NCG + Standard of Care Treatment
Carbaglu Chemical Composition: N-carbamoyl-L-glutamic acid (NCG)
The daily dose will be 150 mg/kg/ day or 3.3 g/m2/day for patients >15 kg and will be administered for 7 days or until discharge, whichever is sooner. The doses are to be divided into 2 equal doses and administered orally or enterally by nasogastric or gastrostomy tube. Standard of care will prevail when choosing the mode of drug administration.
The tablets must be dispersed in a minimum of 2.5-10 ml of water and ingested immediately or administered by fast-push through a syringe via a nasogastric or gastrostomy tube. The suspension has a slightly acidic taste.
Other Name: Carglumic Acid
Drug: Standard of Care Treatment
Active Comparator: Placebo Comparator
Placebo and Standard of Care Therapy
Drug: Standard of Care Treatment
- Trajectory of Change in Ammonia During Hospitalization for Hyperammonemia [ Time Frame: Admission, Post Dialysis, 12, 24, 36, 48 hours and daily for 7 days or until discharge ]Change in ammonia and Functional Status Score (FSS)
- Safety of NCG [ Time Frame: Admission, 12, 24, 36, 48 hours and daily until day 7 after episode (or discharge, whichever is sooner) ]
The primary safety outcome of the study will be the assessed via the rate of Serious Adverse Events (SAEs) defined in this study as death or substantial prolongation of hospitalization, as patients are hospitalized as part of entry to the study.
Safety tests consisting of complete blood count (CBC), liver and kidney function tests, coagulation profile (PTT/INR) will be performed before treatment, on the third day of treatment, and just prior to discontinuation of NCG. A electrocardiogram test will be given before treatment and repeated on the third day of treatment (48 hours following the initial drug administration) or before discharge if earlier, to check for cardiac toxicity.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01599286
|United States, California|
|University of California Los Angeles|
|Los Angeles, California, United States, 90095|
|Lucile Packard Children's Hospital at Stanford|
|Palo Alto, California, United States, 94304|
|United States, Colorado|
|The Children's Hospital of Colorado|
|Aurora, Colorado, United States, 80045|
|United States, District of Columbia|
|Children's National Medical Center|
|Washington, District of Columbia, United States, 20010|
|United States, Massachusetts|
|Children's Hospital Boston|
|Boston, Massachusetts, United States, 02115|
|United States, New York|
|Mount Sinai School of Medicine|
|New York, New York, United States, 10029|
|United States, Ohio|
|University Hospitals Cleveland Medical Center|
|Cleveland, Ohio, United States, 44106|
|United States, Pennsylvania|
|The Children's Hospital of Philadelphia (CHOP)|
|Philadelphia, Pennsylvania, United States, 19104|
|University of Pittsburgh|
|Pittsburgh, Pennsylvania, United States, 15224|
|Principal Investigator:||Mendel Tuchman, MD||Children's Research Institute|