Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| HHSN267200700051C | Other Identifier | NICHD |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Meropenem is an antibiotic that is commonly used to treat serious infections. Although it is used in premature and young infants, the correct dose is not known. The purpose of this study is to determine the correct dose and the safety of meropenem for the treatment of complicated intra-abdominal infections in these young babies.
This study will evaluate the safety, tolerability and Pharmacokinetics - Pharmacodynamics (PK-PD) of meropenem in infants <91 days of age with suspected and complicated intra-abdominal infections.
The specific aims of this trial are:
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Meropenem | Experimental | These Participants were subdivided into the following four groups based on Gestational Age (GA) and Postnatal Age (PNA): 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| meropenem | Drug | Meropenem was administered concomitantly with compatible medications. Because an in-line filter is not appropriate due to drug binding, the 30 minute infusion was rate controlled by using appropriate infusion (syringe) pumps. Dosing and administration of other antimicrobial therapy (e.g., an aminoglycoside) was administered per local standard of care at the discretion of the infant's neonatologist. If there was a delay in the study drug shipment, sites were to use open-label meropenem to protect the safety of the participant. 20 mg/kg every 12 hours in infants <32 weeks GA and PNA < 2 weeks 20 mg/kg every 8 hours in infants <32 weeks GA and PNA ≥ 2 weeks 20 mg/kg every 8 hours in infants ≥32 weeks GA and PNA < 2 weeks 30 mg/kg every 8 hours in infants ≥32 weeks GA and PNA ≥ 2 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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) | 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. | Average of 12 days (3 to 21 days) |
| Deaths | Up to 51 days (Recorded from the time of informed consent until 72 hours following the last dose of study drug) | |
| Meropenem Clearance | 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. | Up to 7-8hrs post drug administration |
| Key Safety Endpoints | 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 | 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) |
Not provided
Not provided
Inclusion Criteria:
Written permission from parent or legal guardian
Age younger than 91 days
Likely to survive beyond the first 48 hours after enrollment
Sufficient intravascular access (either peripheral or central) to receive study drug.
AND ONE OF THE FOLLOWING
1) Physical, radiological, and/or bacteriological findings of a complicated intra-abdominal infection. These include peritonitis, NEC (Necrotizing Enterocolitis) Grade II or higher by Bell's criteria, Hirschsprung's disease with perforation, spontaneous perforation, meconium ileus with perforation, bowel obstruction with perforation, as evidenced by free peritoneal air on abdominal radiograph, intestinal pneumatosis or portal venous gas on abdominal radiographic examination.
OR 2) Possible NEC OR 3) Otherwise receiving meropenem per local standard of care
Exclusion criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Danny Benjamin, MD, PhD, MPH | Duke University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama | Birmingham | Alabama | 35233 | United States | ||
| Children's Hospital of Oakland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22955430 | Derived | Cohen-Wolkowiez M, Poindexter B, Bidegain M, Weitkamp JH, Schelonka RL, Randolph DA, Ward RM, Wade K, Valencia G, Burchfield D, Arrieta A, Mehta V, Walsh M, Kantak A, Rasmussen M, Sullivan JE, Finer N, Rich W, Brozanski BS, van den Anker J, Blumer J, Laughon M, Watt KM, Kearns GL, Capparelli EV, Martz K, Berezny K, Benjamin DK Jr, Smith PB; Meropenem Study Team. Safety and effectiveness of meropenem in infants with suspected or complicated intra-abdominal infections. Clin Infect Dis. 2012 Dec;55(11):1495-502. doi: 10.1093/cid/cis758. Epub 2012 Sep 5. |
Not provided
Not provided
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.
Enrollment Period - June 19, 2008 to October 6, 2009 Locations - Hospitals including University Hospitals Total number of sites - 24 Total number of participants - 200
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 1. GA <32 Wks; PNA<2 Wks | Group 1: GA at birth below 32 weeks - PNA < 2 weeks; |
| FG001 | 2. GA <32 Wks; PNA 91days ≥ 2Wks | Group 2: GA at birth below 32 weeks - PNA ≥ 2 weeks and < 91 days |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
| Oakland |
| California |
| 94609 |
| United States |
| Children's Hospital of Orange County | Orange | California | 92868 | United States |
| University of California Medical Center | San Diego | California | 92117 | United States |
| Sharp-Mary Birch Hospital for Women | San Diego | California | 92123 | United States |
| Yale New Haven Hospital | New Haven | Connecticut | 06510 | United States |
| Children's National Medical Center | Washington D.C. | District of Columbia | 20010 | United States |
| University of Florida | Gainesville | Florida | 32610 | United States |
| Kapiolani Medical Center for Women and Children | Honolulu | Hawaii | 96826 | United States |
| Evanston Northwestern Healthcare | Evanston | Illinois | 60056 | United States |
| Indiana University - Riley Hospital for Children | Indianapolis | Indiana | 46202 | United States |
| University of Louisville | Louisville | Kentucky | 40202 | United States |
| University of Michigan | Ann Arbor | Michigan | 48109 | United States |
| Kansas City Children's Mercy Hospital | Kansas City | Missouri | 64108 | United States |
| Albany Medical Center | Albany | New York | 12208 | United States |
| Suny Downstate Medical Center | Brooklyn | New York | 11203 | United States |
| Duke University Medical Center | Durham | North Carolina | 27708 | United States |
| Duke University | Durham | North Carolina | 27715 | United States |
| Akron Children's Hospital | Akron | Ohio | 44308 | United States |
| Case Western Reserve, RB&C, UHCMC | Cleveland | Ohio | 44106 | United States |
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
| Magee Women's Hospital | Pittsburgh | Pennsylvania | 15213 | United States |
| Vanderbilt Children's Hospital | Nashville | Tennessee | 37232 | United States |
| University of Texas Southwestern Medical Center | Dallas | Texas | 75390 | United States |
| Baylor College of Medicine | Houston | Texas | 77030 | United States |
| University of Utah medical Center | Salt Lake City | Utah | 84108 | United States |
| FG002 | 3. GA ≥ 32 Wks; PNA <2 Wks | Group 3: GA at birth 32 weeks or older - PNA < 2 weeks; |
| FG003 | 4. GA ≥32 Wks; PNA 91 Days ≥ 2 Wks | Group 4: GA at birth 32 weeks or older - PNA ≥ 2 weeks and < 91 days. |
| Safety Population |
|
| Efficacy Population |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 1. GA <32 Wks; PNA<2 Wks | Group 1: GA at birth below 32 weeks - PNA < 2 weeks; |
| BG001 | 2. GA <32 Wks; PNA 91days ≥ 2Wks | Group 2: GA at birth below 32 weeks - PNA ≥ 2 weeks and < 91 days |
| BG002 | 3. GA ≥ 32 Wks; PNA <2 Wks | Group 3: GA at birth 32 weeks or older - PNA < 2 weeks; |
| BG003 | 4. GA ≥32 Wks; PNA 91 Days ≥ 2 Wks | Group 4: GA at birth 32 weeks or older - PNA ≥ 2 weeks and < 91 days. |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Post Natal Age (in days) | Mean | Standard Deviation | Days |
| ||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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) | 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. | 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). | Posted | Number | Participants | Average of 12 days (3 to 21 days) |
|
|
| |||||||||||||||||||||||||||||||||||
| Primary | Deaths | The Safety Population includes all patients who receive any amount of meropenem. | Posted | Number | Participants | Up to 51 days (Recorded from the time of informed consent until 72 hours following the last dose of study drug) |
|
| |||||||||||||||||||||||||||||||||||||
| Primary | Meropenem Clearance | 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. | Posted | Mean | Standard Deviation | L/h/kg | Up to 7-8hrs post drug administration |
| |||||||||||||||||||||||||||||||||||||
| Primary | Key Safety Endpoints | 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 | Safety Population - The Safety Population includes all patients who receive any amount of meropenem. | Posted | Number | Participants | 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) |
|
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.
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.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 1. GA <32 Wks; PNA<2 Wks | Group 1: GA at birth below 32 weeks - PNA < 2 weeks; | 9 | 39 | 9 | 39 | ||
| EG001 | 2. GA <32 Wks; PNA 91days ≥ 2Wks | Group 2: GA at birth below 32 weeks - PNA ≥ 2 weeks and < 91 days | 18 | 103 | 8 | 103 | ||
| EG002 | 3. GA ≥ 32 Wks; PNA <2 Wks | Group 3: GA at birth 32 weeks or older - PNA < 2 weeks; | 2 | 31 | 2 | 31 | ||
| EG003 | 4. GA ≥32 Wks; PNA 91 Days ≥ 2 Wks | Group 4: GA at birth 32 weeks or older - PNA ≥ 2 weeks and < 91 days. | 5 | 27 | 3 | 27 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bradycardia | Cardiac disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Congenital diaphragmatic Hernia | Congenital, familial and genetic disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Patent Ductus Arteriosus | Congenital, familial and genetic disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Retinopathy of Prematurity | Eye disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Colonic Stenosis | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Illeal Perforation | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Intestinal Ischaemia | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Intestinal Obstruction | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Intestinal perforation | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Intestinal Stenosis | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Necrotising Colitis | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Rectal Haemorrhage | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Multi-organ failure | General disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Abdominal Sepsis | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
| |
| Bacterial Sepsis | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
| |
| Fungal Sepsis | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
| |
| Meningitis | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
| |
| Respiratory Synctial Virus Infection | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
| |
| Wound Dehiscence | Injury, poisoning and procedural complications | MedDRA 13.0 | Systematic Assessment |
| |
| Chest X-Ray Abnormal | Investigations | MedDRA 13.0 | Systematic Assessment |
| |
| Subarachnoid Haemorrhage | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Apnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Pneumonia Aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Pulmonary Haemorrhage | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Respiratory Arrest | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Respiratory Distress | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Respiratory Failure | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sepsis | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
| |
| Convulsion | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| David Siegel, MD | Eunice Kennedy Shriver National Institute of Child Health and Human Development | 301-595-8670 | siegelda@mail.nih.gov |
| ID | Term |
|---|---|
| D020345 | Enterocolitis, Necrotizing |
| D059413 | Intraabdominal Infections |
| ID | Term |
|---|---|
| D004760 | Enterocolitis |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D007410 | Intestinal Diseases |
| D007239 | Infections |
Not provided
Not provided
| ID | Term |
|---|---|
| D000077731 | Meropenem |
| ID | Term |
|---|---|
| D013845 | Thienamycins |
| D015780 | Carbapenems |
| D047090 | beta-Lactams |
| D007769 | Lactams |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Participants |
|
|
|
|
|
|