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Trial record 2 of 24 for:    "Enterocolitis" | "Anti-Infective Agents"

Pharmacokinetic (PK) and Safety Study of Meropenem in Young Infants With Intra-abdominal Infections

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ClinicalTrials.gov Identifier: NCT00621192
Recruitment Status : Completed
First Posted : February 22, 2008
Results First Posted : November 29, 2011
Last Update Posted : April 17, 2015
Sponsor:
Collaborator:
The Emmes Company, LLC
Information provided by (Responsible Party):
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Necrotizing Enterocolitis
Intra-abdominal Infection
Intervention Drug: meropenem
Enrollment 200
Recruitment Details Enrollment Period - June 19, 2008 to October 6, 2009 Locations - Hospitals including University Hospitals Total number of sites - 24 Total number of participants - 200
Pre-assignment Details Other antimicrobials in addition to meropenem was used in the study due to concerns regarding the safety and ethics of using monotherapy in this patient population.The study was designed as an open-label, dose escalation study because sufficient data regarding the feasibility of a randomized, active controlled efficacy study was unavailable.
Arm/Group Title 1. GA <32 Wks; PNA<2 Wks 2. GA <32 Wks; PNA 91days ≥ 2Wks 3. GA ≥ 32 Wks; PNA <2 Wks 4. GA ≥32 Wks; PNA 91 Days ≥ 2 Wks
Hide Arm/Group Description Group 1: GA at birth below 32 weeks - PNA < 2 weeks; Group 2: GA at birth below 32 weeks - PNA ≥ 2 weeks and < 91 days Group 3: GA at birth 32 weeks or older - PNA < 2 weeks; Group 4: GA at birth 32 weeks or older - PNA ≥ 2 weeks and < 91 days.
Period Title: Overall Study
Started 39 103 31 27
Safety Population 39 103 31 27
Efficacy Population 39 101 28 27
Completed 35 94 26 24
Not Completed 4 9 5 3
Reason Not Completed
Withdrawal by Subject             0             0             2             0
Physician Decision             1             3             0             0
Protocol Violation             1             0             0             1
Adverse Event             0             1             0             1
Death             2             5             0             0
Final Assessments not Completed             0             0             3             1
Arm/Group Title 1. GA <32 Wks; PNA<2 Wks 2. GA <32 Wks; PNA 91days ≥ 2Wks 3. GA ≥ 32 Wks; PNA <2 Wks 4. GA ≥32 Wks; PNA 91 Days ≥ 2 Wks Total
Hide Arm/Group Description Group 1: GA at birth below 32 weeks - PNA < 2 weeks; Group 2: GA at birth below 32 weeks - PNA ≥ 2 weeks and < 91 days Group 3: GA at birth 32 weeks or older - PNA < 2 weeks; Group 4: GA at birth 32 weeks or older - PNA ≥ 2 weeks and < 91 days. Total of all reporting groups
Overall Number of Baseline Participants 39 103 31 27 200
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Days
Mean Postnatal Age Number Analyzed 39 participants 103 participants 31 participants 27 participants 200 participants
8.5  (3.3) 38.3  (19.3) 6.5  (3.5) 36.0  (22.0) 27.3  (21.6)
[1]
Measure Description: Post Natal Age
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 39 participants 103 participants 31 participants 27 participants 200 participants
Female
15
  38.5%
47
  45.6%
9
  29.0%
11
  40.7%
82
  41.0%
Male
24
  61.5%
56
  54.4%
22
  71.0%
16
  59.3%
118
  59.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 39 participants 103 participants 31 participants 27 participants 200 participants
Hispanic or Latino
5
  12.8%
16
  15.5%
4
  12.9%
3
  11.1%
28
  14.0%
Not Hispanic or Latino
32
  82.1%
81
  78.6%
27
  87.1%
24
  88.9%
164
  82.0%
Unknown or Not Reported
2
   5.1%
6
   5.8%
0
   0.0%
0
   0.0%
8
   4.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 39 participants 103 participants 31 participants 27 participants 200 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
1
   1.0%
0
   0.0%
1
   3.7%
2
   1.0%
Native Hawaiian or Other Pacific Islander
1
   2.6%
0
   0.0%
1
   3.2%
0
   0.0%
2
   1.0%
Black or African American
12
  30.8%
33
  32.0%
8
  25.8%
5
  18.5%
58
  29.0%
White
25
  64.1%
65
  63.1%
21
  67.7%
18
  66.7%
129
  64.5%
More than one race
1
   2.6%
2
   1.9%
0
   0.0%
2
   7.4%
5
   2.5%
Unknown or Not Reported
0
   0.0%
2
   1.9%
1
   3.2%
1
   3.7%
4
   2.0%
1.Primary Outcome
Title Efficacy Success (Alive at Efficacy Visit,Last Culture (if Obtained) From Sterile Body Fluid is Negative for Bacteria (Except Staphylococcus Species) From Start of Study Drug Until Efficacy Visit,Presumptive Clinical Cure Score(PCCS) >7 at Efficacy Visit)
Hide Description

The PCCS was derived by comparing clinical signs and symptoms prior to administration of the first dose of study drug and study Day 28.The elements of the PCCS include Mean BP,Temp,PaO2(mmHg)/FiO2,Lowest serum pH,seizures,Urine output,Cardiovascular inotrope support,C-reactive protein (CRP)and Abdominal girth.

Score - Asymptomatic to Asymptomatic 1;Asymptomatic to Worsening 0;Symptomatic to Worsening 0;Symptomatic to No change 0;Symptomatic to Improved 1;Symptomatic to Asymptomatic 1

If 7 or more of 10 signs received a score of 1, then the infant was considered a presumptive clinical cure.

GA stands for Gestational Age and PNA stands for Postnatal Age.

Time Frame Average of 12 days (3 to 21 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The Efficacy Population includes all patients who have efficacy assessment (Clinical Signs) at Pre-Dose and Study Day 28 (or the day that the Day 28 assessments were taken).
Arm/Group Title 1. GA <32 Wks; PNA<2 Wks 2. GA <32 Wks; PNA 91days ≥ 2Wks 3. GA ≥ 32 Wks; PNA <2 Wks 4. GA ≥32 Wks; PNA 91 Days ≥ 2 Wks
Hide Arm/Group Description:
Group 1: GA at birth below 32 weeks - PNA < 2 weeks;
Group 2: GA at birth below 32 weeks - PNA ≥ 2 weeks and < 91 days
Group 3: GA at birth 32 weeks or older - PNA < 2 weeks;
Group 4: GA at birth 32 weeks or older - PNA ≥ 2 weeks and < 91 days.
Overall Number of Participants Analyzed 39 98 28 27
Measure Type: Number
Unit of Measure: Participants
29 82 26 25
2.Primary Outcome
Title Deaths
Hide Description [Not Specified]
Time Frame Up to 51 days (Recorded from the time of informed consent until 72 hours following the last dose of study drug)
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Population includes all patients who receive any amount of meropenem.
Arm/Group Title 1. GA <32 Wks; PNA<2 Wks 2. GA <32 Wks; PNA 91days ≥ 2Wks 3. GA ≥ 32 Wks; PNA <2 Wks 4. GA ≥32 Wks; PNA 91 Days ≥ 2 Wks
Hide Arm/Group Description:
Group 1: GA at birth below 32 weeks - PNA < 2 weeks;
Group 2: GA at birth below 32 weeks - PNA ≥ 2 weeks and < 91 days
Group 3: GA at birth 32 weeks or older - PNA < 2 weeks;
Group 4: GA at birth 32 weeks or older - PNA ≥ 2 weeks and < 91 days.
Overall Number of Participants Analyzed 39 103 31 27
Measure Type: Number
Unit of Measure: Participants
3 8 0 0
3.Primary Outcome
Title Meropenem Clearance
Hide Description Given the limited availability of blood for Pharmacokinetic (PK) assessments in this population a sparse sampling approach was utilized. Subjects were assigned to one of two Dose 1 sample collection schedules, “PK-odd” and “PK-even” based on birth date to ensure collection of PK data throughout the dose interval. In addition, PK samples were collected around approximately the 5th dose. Subjects that did not have Dose 1 PK samples could have steady-state (Dose 5) using the Dose 5 PK collection schedule.
Time Frame Up to 7-8hrs post drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 1. GA <32 Wks; PNA<2 Wks 2. GA <32 Wks; PNA 91days ≥ 2Wks 3. GA ≥ 32 Wks; PNA <2 Wks 4. GA ≥32 Wks; PNA 91 Days ≥ 2 Wks
Hide Arm/Group Description:
Group 1: GA at birth below 32 weeks - PNA < 2 weeks;
Group 2: GA at birth below 32 weeks - PNA ≥ 2 weeks and < 91 days
Group 3: GA at birth 32 weeks or older - PNA < 2 weeks;
Group 4: GA at birth 32 weeks or older - PNA ≥ 2 weeks and < 91 days.
Overall Number of Participants Analyzed 39 98 28 27
Mean (Standard Deviation)
Unit of Measure: L/h/kg
0.089  (0.027) 0.122  (0.037) 0.135  (0.040) 0.202  (0.061)
4.Primary Outcome
Title Key Safety Endpoints
Hide Description Safety assessments included death, seizure documentation (including correlation of serum meropenem level and seizures), strictures, perforation, wound dehiscence, short gut, development of extended beta lactamase infection, development of candidiasis, antimicrobial therapy failure
Time Frame Up to 51 days (Adverse Events (AEs) were recorded from the time of informed consent until 72 hours following the last dose of study drug)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population - The Safety Population includes all patients who receive any amount of meropenem.
Arm/Group Title 1. GA <32 Wks; PNA<2 Wks 2. GA <32 Wks; PNA 91days ≥ 2Wks 3. GA ≥ 32 Wks; PNA <2 Wks 4. GA ≥32 Wks; PNA 91 Days ≥ 2 Wks
Hide Arm/Group Description:
Group 1: GA at birth below 32 weeks - PNA < 2 weeks;
Group 2: GA at birth below 32 weeks - PNA ≥ 2 weeks and < 91 days
Group 3: GA at birth 32 weeks or older - PNA < 2 weeks;
Group 4: GA at birth 32 weeks or older - PNA ≥ 2 weeks and < 91 days.
Overall Number of Participants Analyzed 39 103 31 27
Measure Type: Number
Unit of Measure: Participants
Death 3 8 0 0
Seizure 4 3 1 2
Strictures 0 0 0 0
Perforation 2 2 0 0
Wound Dehiscence 1 1 1 1
Development of Candidiasis 5 3 0 0
Antimicrobial Therapy Failure 7 12 2 2
Time Frame Adverse Events (AEs) were recorded from the time of informed consent until 72 hours following the last dose of study drug for non-Serious Adverse Events (SAEs) and until 30 days after the last dose of study drug for SAEs.
Adverse Event Reporting Description

Any AE that occurred between the time informed consent was obtained and the initial dose of study, that was considered related to a protocol specified procedure, were reported.

The Investigator was responsible for assessing relationship of AE to study medication using the following definitions:Not related, possibly, probably or definitely related.

 
Arm/Group Title 1. GA <32 Wks; PNA<2 Wks 2. GA <32 Wks; PNA 91days ≥ 2Wks 3. GA ≥ 32 Wks; PNA <2 Wks 4. GA ≥32 Wks; PNA 91 Days ≥ 2 Wks
Hide Arm/Group Description Group 1: GA at birth below 32 weeks - PNA < 2 weeks; Group 2: GA at birth below 32 weeks - PNA ≥ 2 weeks and < 91 days Group 3: GA at birth 32 weeks or older - PNA < 2 weeks; Group 4: GA at birth 32 weeks or older - PNA ≥ 2 weeks and < 91 days.
All-Cause Mortality
1. GA <32 Wks; PNA<2 Wks 2. GA <32 Wks; PNA 91days ≥ 2Wks 3. GA ≥ 32 Wks; PNA <2 Wks 4. GA ≥32 Wks; PNA 91 Days ≥ 2 Wks
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
1. GA <32 Wks; PNA<2 Wks 2. GA <32 Wks; PNA 91days ≥ 2Wks 3. GA ≥ 32 Wks; PNA <2 Wks 4. GA ≥32 Wks; PNA 91 Days ≥ 2 Wks
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/39 (23.08%)      18/103 (17.48%)      2/31 (6.45%)      5/27 (18.52%)    
Cardiac disorders         
Bradycardia  1  1/39 (2.56%)  1 0/103 (0.00%)  0 0/31 (0.00%)  0 0/27 (0.00%)  0
Congenital, familial and genetic disorders         
Congenital diaphragmatic Hernia  1  0/39 (0.00%)  0 1/103 (0.97%)  1 0/31 (0.00%)  0 0/27 (0.00%)  0
Patent Ductus Arteriosus  1  0/39 (0.00%)  0 0/103 (0.00%)  0 0/31 (0.00%)  0 1/27 (3.70%)  1
Eye disorders         
Retinopathy of Prematurity  1  0/39 (0.00%)  0 1/103 (0.97%)  1 0/31 (0.00%)  0 0/27 (0.00%)  0
Gastrointestinal disorders         
Colonic Stenosis  1  0/39 (0.00%)  0 1/103 (0.97%)  1 0/31 (0.00%)  0 0/27 (0.00%)  0
Illeal Perforation  1  1/39 (2.56%)  1 0/103 (0.00%)  0 0/31 (0.00%)  0 0/27 (0.00%)  0
Intestinal Ischaemia  1  0/39 (0.00%)  0 1/103 (0.97%)  1 0/31 (0.00%)  0 0/27 (0.00%)  0
Intestinal Obstruction  1  0/39 (0.00%)  0 0/103 (0.00%)  0 0/31 (0.00%)  0 1/27 (3.70%)  1
Intestinal perforation  1  2/39 (5.13%)  2 2/103 (1.94%)  2 0/31 (0.00%)  0 0/27 (0.00%)  0
Intestinal Stenosis  1  0/39 (0.00%)  0 0/103 (0.00%)  0 0/31 (0.00%)  0 1/27 (3.70%)  1
Necrotising Colitis  1  2/39 (5.13%)  2 1/103 (0.97%)  1 0/31 (0.00%)  0 0/27 (0.00%)  0
Rectal Haemorrhage  1  0/39 (0.00%)  0 0/103 (0.00%)  0 1/31 (3.23%)  1 0/27 (0.00%)  0
General disorders         
Multi-organ failure  1  2/39 (5.13%)  2 2/103 (1.94%)  2 0/31 (0.00%)  0 0/27 (0.00%)  0
Infections and infestations         
Abdominal Sepsis  1  0/39 (0.00%)  0 1/103 (0.97%)  1 0/31 (0.00%)  0 0/27 (0.00%)  0
Bacterial Sepsis  1  0/39 (0.00%)  0 1/103 (0.97%)  1 0/31 (0.00%)  0 0/27 (0.00%)  0
Fungal Sepsis  1  0/39 (0.00%)  0 1/103 (0.97%)  1 0/31 (0.00%)  0 0/27 (0.00%)  0
Meningitis  1  0/39 (0.00%)  0 1/103 (0.97%)  1 0/31 (0.00%)  0 0/27 (0.00%)  0
Respiratory Synctial Virus Infection  1  0/39 (0.00%)  0 1/103 (0.97%)  1 0/31 (0.00%)  0 0/27 (0.00%)  0
Sepsis  1  1/39 (2.56%)  1 1/103 (0.97%)  1 0/31 (0.00%)  0 0/27 (0.00%)  0
Injury, poisoning and procedural complications         
Wound Dehiscence  1  0/39 (0.00%)  0 1/103 (0.97%)  1 0/31 (0.00%)  0 0/27 (0.00%)  0
Investigations         
Chest X-Ray Abnormal  1  0/39 (0.00%)  0 0/103 (0.00%)  0 0/31 (0.00%)  0 1/27 (3.70%)  1
Nervous system disorders         
Subarachnoid Haemorrhage  1  1/39 (2.56%)  1 0/103 (0.00%)  0 0/31 (0.00%)  0 0/27 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Apnoea  1  0/39 (0.00%)  0 0/103 (0.00%)  0 1/31 (3.23%)  1 0/27 (0.00%)  0
Pneumonia Aspiration  1  0/39 (0.00%)  0 0/103 (0.00%)  0 0/31 (0.00%)  0 1/27 (3.70%)  1
Pulmonary Haemorrhage  1  0/39 (0.00%)  0 1/103 (0.97%)  1 0/31 (0.00%)  0 0/27 (0.00%)  0
Respiratory Arrest  1  1/39 (2.56%)  1 0/103 (0.00%)  0 0/31 (0.00%)  0 0/27 (0.00%)  0
Respiratory Distress  1  0/39 (0.00%)  0 0/103 (0.00%)  0 0/31 (0.00%)  0 1/27 (3.70%)  1
Respiratory Failure  1  0/39 (0.00%)  0 1/103 (0.97%)  1 0/31 (0.00%)  0 0/27 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
1. GA <32 Wks; PNA<2 Wks 2. GA <32 Wks; PNA 91days ≥ 2Wks 3. GA ≥ 32 Wks; PNA <2 Wks 4. GA ≥32 Wks; PNA 91 Days ≥ 2 Wks
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/39 (23.08%)      8/103 (7.77%)      2/31 (6.45%)      3/27 (11.11%)    
Infections and infestations         
Sepsis  1  5/39 (12.82%)  12 5/103 (4.85%)  12 1/31 (3.23%)  12 1/27 (3.70%)  12
Nervous system disorders         
Convulsion  1  4/39 (10.26%)  10 3/103 (2.91%)  10 1/31 (3.23%)  10 2/27 (7.41%)  10
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: David Siegel, MD
Organization: Eunice Kennedy Shriver National Institute of Child Health and Human Development
Phone: 301-595-8670
EMail: siegelda@mail.nih.gov
Layout table for additonal information
Responsible Party: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier: NCT00621192     History of Changes
Other Study ID Numbers: HHSN267200700051C
HHSN267200700051C ( Other Identifier: NICHD )
First Submitted: February 20, 2008
First Posted: February 22, 2008
Results First Submitted: October 20, 2011
Results First Posted: November 29, 2011
Last Update Posted: April 17, 2015