Short-Term Outcome of N-Carbamylglutamate in the Treatment of Acute Hyperammonemia (STO)
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|ClinicalTrials.gov Identifier: NCT01599286|
Recruitment Status : Completed
First Posted : May 16, 2012
Results First Posted : February 15, 2021
Last Update Posted : February 15, 2021
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||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)|
|Actual Enrollment :||35 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 1, 2012|
|Actual Primary Completion Date :||April 30, 2019|
|Actual 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
Active Comparator: Placebo Comparator
Placebo and Standard of Care Therapy
Placebo that looks/tastes the same as NCG and is administered on the same schedule as the NCG intervention
- Time to the Primary Outcome (Earlier of Ammonia <50 µmol/L or Hospital Discharge) [ Time Frame: Average of all measurements of hyperammonemia, for up to 7 days ]The composite primary intention to treat (ITT) outcome of the earlier of time to reach an ammonia level of ≤50 µmol/L or hospital discharge. Data presented as a hazard ratio based on the time to reach an ammonia level of ≤50 µmol/L. The outcome measure was a survival analysis based on time to reach the earlier of an ammonia level of ≤50 µmol/L or time to discharge, which was considered to be a point where the patient was no longer at risk of neurological injury from ammonia. The outcome of survival analysis was a hazard ratio reflecting the ratio of probabilities in each group (drug vs placebo) of reaching the earlier of an ammonia level of ≤50 µmol/L or discharge. We measured multiple post-treatment ammonia levels at uncontrolled times during an episode, so it is difficult to compute a meaningful average that would not be biased by the frequency and timing of ammonia testing during episodes.
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 National Research Institute|