Dalbavancin for the Treatment of Acute Bacterial Skin and Skin Structure Infections in Children, Known or Suspected to be Caused by Susceptible Gram-positive Organisms, Including MRSA

NCT ID: NCT02814916

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 199 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-30
• Study Completion Date: 2024-01-01

Brief Summary

To determine the safety and descriptive efficacy of dalbavancin for the treatment of acute bacterial skin and skin structure infections in children, aged birth to 17 years (inclusive), known or suspected to be caused by susceptible Gram-positive organisms, including methicillin-resistant strains of Staphylococcus aureus.

Conditions

Methicillin-Resistant Staphylococcus Aureus; Bacterial Infections; Staphylococcal Skin Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dalbavancin single-dose

Participants received dalbavancin administered intravenously as follows: birth to \< 3 months old and 3 months to \< 6 years old: 22.5 mg/kg (maximum 1500 mg) on Day 1; ≥6 years to 17 years old (inclusive): 18 mg/kg (maximum 1500 mg) on Day 1. Participants aged birth to \< 3 months were not randomized; all received dalbavancin single-dose.

Group Type: EXPERIMENTAL

Dalbavancin

Intervention Type: DRUG

Dalbavancin was administered intravenously over 30 (± 5) minutes.

Dalbavancin two-dose

Participants received dalbavancin administered intravenously as follows: 3 months to \< 6 years old: 15 mg/kg (maximum 1000 mg) on Day 1, and 7.5 mg/kg (maximum 500 mg) on Day 8; ≥6 years to 17 years old (inclusive): 12 mg/kg (maximum 1000 mg) on Day 1, and 6 mg/kg (maximum 500 mg) on Day 8.

Group Type: EXPERIMENTAL

Dalbavancin

Intervention Type: DRUG

Dalbavancin was administered intravenously over 30 (± 5) minutes.

Comparator

Participants 3 mos to \< 6 yrs old and ≥6 yrs to 17 yrs old received a 10-14 day course of either vancomycin 10 to 15 mg/kg/dose, not to exceed a 4000 mg total daily dose; or oxacillin 30 mg/kg/dose, infused over 60 (± 10) mins every 6 (± 1) hrs; or flucloxacillin 50 mg/kg/dose, infused over 60 (± 10) mins every 6 (± 1) hrs, not to exceed a 2000 mg total daily dose. Vancomycin was to be taken for methicillin-resistant Gram-positive infections. Based on local practice patterns/approvals for clinical use in the pediatric population, oxacillin or flucloxacillin were supplied as an IV comparator. At investigator's discretion, after 72 hrs of IV therapy, those on oxacillin or flucloxacillin could switch to oral cefadroxil (dose for infants/children: 15 mg/kg/dose every 12 hrs, max 2 g/day; dose for adolescents: 500-1000 mg every 12 hrs), and if infection with methicillin-resistant S. aureus was confirmed, those on vancomycin were allowed to switch to oral clindamycin 10 mg/kg every 8 hrs.

Group Type: ACTIVE_COMPARATOR

Vancomycin

Intervention Type: DRUG

Vancomycin was administered intravenously over 60 (± 10) minutes every 6 (± 1) hours.

Oxacillin

Intervention Type: DRUG

Oxacillin was administered intravenously over 60 (± 10) minutes every 6 (± 1) hours.

Flucloxacillin

Intervention Type: DRUG

Flucloxacillin was administered intravenously over 60 (± 10) minutes every 6 (± 1) hours.

Cefadroxil

Intervention Type: DRUG

Cefadroxil was administered orally every 12 hours.

Clindamycin

Intervention Type: DRUG

Clindamycin was administered orally every 8 hours.

Interventions

Dalbavancin

Dalbavancin was administered intravenously over 30 (± 5) minutes.

Intervention Type: DRUG

Vancomycin

Vancomycin was administered intravenously over 60 (± 10) minutes every 6 (± 1) hours.

Intervention Type: DRUG

Oxacillin

Oxacillin was administered intravenously over 60 (± 10) minutes every 6 (± 1) hours.

Intervention Type: DRUG

Flucloxacillin

Flucloxacillin was administered intravenously over 60 (± 10) minutes every 6 (± 1) hours.

Intervention Type: DRUG

Cefadroxil

Cefadroxil was administered orally every 12 hours.

Intervention Type: DRUG

Clindamycin

Clindamycin was administered orally every 8 hours.

Intervention Type: DRUG

Other Intervention Names

Xydalba

Eligibility Criteria

Inclusion Criteria

• Male or female patients birth to 17 years (inclusive)
• A clinical picture compatible with Acute Bacterial Skin and Skin Structure Infections (ABSSSI) suspected or confirmed to be caused by Gram-positive bacteria, including Methicillin-resistant Staphylococcus aureus (MRSA).
• In addition to local signs of ABSSSI, the patient has at least one of the following:
• Fever, defined as body temperature ≥ 38.4°C (101.2°F) taken orally, ≥ 38.7°C (101.6°F) tympanically, or ≥ 39°C (102.2°F) rectally (core temperature) OR
• Leukocytosis (WBC > 10,000 mm3) or leukopenia (WBC < 2,000 mm3) or left shift of >10% band neutrophils
• Infection either involving deeper soft tissue or requiring significant surgical intervention
• Major cutaneous abscess characterized as a collection of pus within the dermis or deeper that is accompanied by erythema, edema and/or induration which i. requires surgical incision and drainage, and ii. is associated with cellulitis such that the total affected area involves at least 35 cm2 of erythema, or total affected area of erythema is at least BSA (m2) x 43.0 (cm2/m2), OR iii. alternatively, involves the central face and is associated with an area of erythema of at least 15 cm2 b. Surgical site or traumatic wound infection characterized by purulent drainage with surrounding erythema, edema and/or induration which occurred within 30 days after the trauma or surgery and is associated with cellulitis such that: i. the total affected area involves at least 35 cm2 of erythema, or total affected area of erythema is at least BSA (m2) x 43.0 (cm2/m2), OR ii. alternatively, involves the central face and is associated with an affected area of at least 15 cm2 c. Cellulitis, defined as a diffuse skin infection characterized by spreading areas of erythema, edema and/or induration and: i. is associated with erythema that involves at least 35 cm2 of surface area, or surface area of erythema is at least BSA (m2) x 43.0 (cm2/m2), OR ii. alternatively, cellulitis of the central face that is associated with an affected area of at least 15 cm2 5. In addition to the requirement for erythema, all patients are required to have at least two (2) of the following signs of ABSSSI: a. Purulent drainage/discharge b. Fluctuance c. Heat/localized warmth d. Tenderness to palpation e. Swelling/induration

1. Male or female patients from birth to < 3 months of age, including pre-term neonates (gestational age ≥ 32 weeks)

2. A clinical picture compatible with an ABSSSI suspected or confirmed to be caused by Gram-positive bacteria, including MRSA.

OR

Suspected or confirmed sepsis including any of the following clinical criteria:

1. Hypothermia (<36°C) OR fever (>38.5°C)

2. Bradycardia OR tachycardia OR rhythm instability

3. Hypotension OR mottled skin OR impaired peripheral perfusion

4. Petechial rash

5. New onset or worsening of apnea episodes OR tachypnea episodes OR increased oxygen requirements OR requirement for ventilation support

6. Feeding intolerance OR poor sucking OR abdominal distension

7. Irritability

8. Lethargy

9. Hypotonia

3. In addition, patients must meet at least one of the following laboratory criteria:

a. White blood cell count ≤4.0 × 10^9/L OR ≥20.0 × 10^9/L b, Immature to total neutrophil ratio >0.2 c. Platelet count ≤100 × 10^9/L d. C-reactive protein (CRP) >15 mg/L OR procalcitonin ≥ 2 ng/mL e. Hyperglycemia OR Hypoglycemia f. Metabolic acidosis

4. Infections must be of sufficient severity to merit hospitalization and parenteral antibiotic therapy. These infections may include:

1. Cutaneous or subcutaneous abscess

2. Surgical site or traumatic wound infection

3. Cellulitis, Erysipelas

4. Omphalitis

5. Impetigo and bullous impetigo

6. Pustular folliculitis

7. Scarlet fever

8. Staphylococcal scalded skin syndrome

9. Streptococcal toxic shock syndrome

10. Erythematous based-erosion

11. Other infections originating in the skin or subcutaneous tissue and associated with signs and symptoms of sepsis as defined in Inclusion Criterion 2.

5. Patients must be expected to survive with appropriate antibiotic therapy and appropriate supportive care throughout the study.

Exclusion Criteria

1. Patients age 3 months to 17 years: Clinically significant renal impairment, defined as calculated creatinine clearance of less than 30 mL/min. (calculated by the Schwartz "bedside" formula). Patients birth to < 3 months of age: Moderate or severe renal impairment defined as serum creatinine ≥ 2 times the upper limit of normal (× ULN) for age OR urine output < 0.5 mL/kg/h (measured over at least 8 hours prior to dosing) OR requirement for dialysis.

2. Clinically significant hepatic impairment, defined as serum bilirubin or alkaline phosphatase greater than 2 times the upper limits of normal (ULN) for age, and/or serum aspartate aminotransferase (AST) or alanine transaminase (ALT) greater than 3 times the upper limits of normal (ULN) for age.

3. Treatment with an investigational drug within 30 days preceding the first dose of study medication.

4. Patients with sustained shock defined as systolic blood pressure < 90 mm Hg in children ≥ 10 years old, < 70 mm Hg + [2 x age in years] in children 1 to <10 years, or < 70 mmHg in infants 3 to <12 months old for more than 2 hours despite adequate fluid resuscitation, with evidence of hypoperfusion or need for sympathomimetic agents to maintain blood pressure.

5. More than 24 hours of any systemic antibacterial therapy within 96 hours before randomization. EXCEPTION: Microbiological or clinical treatment failure with a systemic antibiotic other than IV study drug that was administered for at least 48 hours. Failure must be confirmed by either a microbiological laboratory report or documented worsening clinical signs or symptoms.

6. Infection due to an organism known prior to study entry to be resistant to dalbavancin (dalbavancin minimum inhibitory concentration (MIC) greater than 0.25 ug/mL) or vancomycin (vancomycin minimum inhibitory concentration (MIC) greater than 2 ug/mL).

7. Patients with necrotizing fasciitis, or deep-seated infections that would require > 2 weeks of antibiotics (e.g., endocarditis, osteomyelitis or septic arthritis).

8. Infections caused exclusively by Gram-negative bacteria (without Gram-positive bacteria present) and infections caused by fungi, whether alone or in combination with a bacterial pathogen.

9. Venous catheter entry site infection.

10. Infections involving diabetic foot ulceration, perirectal abscess or a decubitus ulcer.

11. Patient with an infected device, even if the device is removed. Examples include infection of: prosthetic cardiac valve, vascular graft, a pacemaker battery pack, joint prosthesis, implantable pacemaker or defibrillator, intraaortic balloon pump, left ventricular assist device, or a neurosurgical device such as a ventricular peritoneal shunt, intra-cranial pressure monitor, or epidural catheter.

12. Gram-negative bacteremia, even in the presence of Gram-positive infection or Gram-positive bacteremia. Note: If a Gram-negative bacteremia develops during the study, or is subsequently found to have been present at Baseline, the patient should be removed from study treatment and receive appropriate antibiotic(s) to treat the Gram-negative bacteremia.

13. Patients whose skin infection is the result of having sustained full or partial thickness burns.

14. Patients age 3 months to 17 years, with uncomplicated skin infections such as superficial/simple cellulitis/erysipelas, impetiginous lesion, furuncle, or simple abscess that only requires surgical drainage for cure. Patients birth to < 3 months of age may be enrolled if they have uncomplicated skin infections of sufficient severity to require hospitalization and parenteral antibiotic therapy.

15. Patients age 3 months to 17 years: Concomitant condition requiring any antibiotic therapy that would interfere with the assessment of study drug for the condition under study.

16. Sickle cell anemia

17. Cystic fibrosis

18. Anticipated need of antibiotic therapy for longer than 14 days.

19. Patients who are placed in a hyperbaric chamber as adjunctive therapy for the ABSSSI.

20. More than 2 surgical interventions (defined as procedures conducted under sterile technique and typically unable to be performed at the bedside) for the skin infection, or patients who are expected to require more than 2 such interventions.

21. Medical conditions in which chronic inflammation may preclude assessment of clinical response to therapy even after successful treatment (e.g., chronic stasis dermatitis of the lower extremity).

22. Immunosuppression/immune deficiency, including hematologic malignancy, recent bone marrow transplant (in post-transplant hospital stay), absolute neutrophil count < 500 cells/mm3, receiving immunosuppressant drugs after organ transplantation, receiving oral steroids ≥ 20 mg prednisolone per day (or equivalent) for > 14 days prior to enrollment, and known or suspected human immunodeficiency virus (HIV) infected patients with a CD4 cell count< 200 cells/mm3 or with a past or current acquired immunodeficiency syndrome (AIDS)-defining condition and unknown CD4 count.

23. Known or suspected hypersensitivity to glycopeptide antibiotics, betalactam agents, aztreonam, or cephalosporins.

24. Patients with a rapidly fatal illness, who are not expected to survive for 3 months.

25. Positive urine (or serum) pregnancy test at screening (post-menarchal females only) or after admission (prior to dosing).

26. Pregnant or nursing females; sexually active females of childbearing potential who are unwilling or unable to use adequate contraceptive precautions. Female patients to have pregnancy testing are those who are at least 10 years old with menarche and/or thelarche (beginning of breast development).

• Minimum Eligible Age: 0 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

ABBVIE INC.

Role: STUDY_DIRECTOR

AbbVie

Locations

University of South Alabama /ID# 237446

Mobile, Alabama, United States

Valleywise Health Medical Center /ID# 234343

Phoenix, Arizona, United States

Southbay Pharma Research /ID# 235700

La Palma, California, United States

University of California, Los Angeles /ID# 237533

Los Angeles, California, United States

Duplicate_Children's Hospital Colorado /ID# 237622

Aurora, Colorado, United States

Global Research Holdings LLC /ID# 235747

Panama City, Florida, United States

Tampa General Hospital /ID# 237061

Tampa, Florida, United States

Children's Healthcare of Atlanta - Ferry Rd /ID# 237003

Atlanta, Georgia, United States

University of Maryland Medical Center /ID# 234353

Baltimore, Maryland, United States

Duplicate_Children's Mercy Hospital and Clinics /ID# 237800

Kansas City, Missouri, United States

Robert Wood Johnson Univ Hosp /ID# 237862

New Brunswick, New Jersey, United States

NYU School of Medicine /ID# 236783

New York, New York, United States

SUNY Upstate Medical University /ID# 236831

Syracuse, New York, United States

Duke University Medical Center /ID# 234315

Durham, North Carolina, United States

Cleveland Clinic Main Campus /ID# 237564

Cleveland, Ohio, United States

Hospital de Ninos Dr. Orlando Alassia /ID# 235562

Santa Fe, , Argentina

Grodno Regional Infectious Disease Hospital /ID# 235661

Grodno, , Belarus

Mogilev Regional Children's Hospital /ID# 235657

Mogilev, , Belarus

Vitebsk Regional Clinical Center for Children /ID# 235659

Vitebsk, , Belarus

Duplicate_Hospital Pequeno Princípe /ID# 235629

Curitiba, Paraná, Brazil

Duplicate_Irmandade Santa Casa de Misericórdia de Porto Alegre /ID# 235627

Porto Alegre, Rio Grande do Sul, Brazil

University Multiprofile Hospital for Active Treatment Deva Maria EOOD Burgas /ID# 235965

Bulgas, , Bulgaria

MHAT (Multiprofile Hospital for Active Treatment) /ID# 235539

Kozloduy, , Bulgaria

UMHAT Dr Georgi Stranski EAD /ID# 237829

Pleven, , Bulgaria

UMHAT Dr Georgi Stranski EAD /ID# 237830

Pleven, , Bulgaria

Multiprofile Hospital for Active Treatment ( UMHAT) Sveti Georgi EAD Plovdiv /ID# 235487

Plovdiv, , Bulgaria

UMHAT Sveti Georgi /ID# 237026

Plovdiv, , Bulgaria

UMHAT Kanev /ID# 237809

Rousse, , Bulgaria

Medical center 1 Sevlievo /ID# 237470

Sevlievo, , Bulgaria

MHATEM N.I.Pirogov Septic Surgery Clinic /ID# 235541

Sofia, , Bulgaria

SHAT Hematologic Diseases /ID# 237915

Sofia, , Bulgaria

University Multiprofile Hospital for Active Treatment Prof. Dr. Stoyan Kirkovich /ID# 235543

Stara Zagora, , Bulgaria

Hospital de Ninos Dr. Roberto del Rio /ID# 235568

Independencia, , Chile

Hospital El Carmen de Maipú /ID# 235570

Santiago, , Chile

Fundacion Cardioinfantil /Id# 238041

Bogota, Cundinamarca, Colombia

Unidad De Investigacion Clinica Universidad De La Sabana /ID# 235566

Chía, Cundinamarca, Colombia

Hospital Universitario San Vic /ID# 238117

Medellín, , Colombia

LTD Unimedi Kakheti Batumi Maternal and Child Healthcare Center /ID# 235643

Batumi, , Georgia

LEPL Tbilisi State Medical University Givi Zhvania Academic Clinic of Pediatry /ID# 235645

Tbilisi, , Georgia

LTD M. Iashvili Children's Central Hospital /ID# 235639

Tbilisi, , Georgia

LTD Unimedi Kakheti Children New Hospital /ID# 235634

Tbilisi, , Georgia

University General Hospital Attikon /ID# 237398

Athens, Attica, Greece

Papageorgiou General Hospital Thessaloniki /ID# 237505

Stavroupoli (Thessalonikis), Thessaloniki, Greece

Childrens Hospital of Penteli /ID# 235667

Athens, , Greece

General Hospital of Thessaloniki Hippokrateio /ID# 237186

Thessaloniki, , Greece

Hospital Valle del Sol /ID# 235569

Guatemala City, , Guatemala

Hospital Roosevelt /ID# 235520

Guatemala City, , Guatemala

Hospital del Centro Medico Infectology Department /ID# 235522

Guatemala City, , Guatemala

Daugavpils Regional Hospital /ID# 237022

Daugavpils, , Latvia

Liepaja Regional Hospital /ID# 235650

Liepāja, , Latvia

University Childrens Hospital /ID# 235648

Riga, , Latvia

Hospital of Lithuanian University of Health Sciences Kaunas Clinics /ID# 236947

Kaunas, , Lithuania

Klaipeda Children's Hospital /ID# 235652

Klaipėda, , Lithuania

Duplicate_Children's Hospital Affiliate - Vilnius University Hospital Santariski /ID# 235654

Vilnius, , Lithuania

Instituto Nacional de Pediatria /ID# 235506

Coyoacán, Mexico City, Mexico

Hospital Universitario Dr. Jose Eleuterio Gonzalez /ID# 237597

Monterrey, Nuevo León, Mexico

Hospital General Dr. Agustin O'Horan /ID# 235510

Mérida, Yucatán, Mexico

Hospital Infantil de Mexico Federico Gomez /ID# 235508

Mexico City, , Mexico

Hospital Materno Infantil José Domingo de Obaldía /ID# 235625

Chiriquí, Chiriquí Province, Panama

Hospital Del Niño Dr. José Renán Esquivel /ID# 235572

Panama City, , Panama

Wojewodzki Szpital Obserwacyjno-Zakazny im. Tadeusza Browicza /ID# 236920

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland

Panstwowy Instytut Medyczny MSWiA w Warszawie /ID# 237112

Warsaw, Masovian Voivodeship, Poland

Specjalistyczny ZOZ nad Matka i Dzieckiem w Poznaniu Oddzial Obserwacyjno /ID# 235518

Poznan, , Poland

Institutul National de Boli Infectioase Prof. Dr. Matei Bals /ID# 235606

Sector 2, București, Romania

Spitalul Clinic de Urgenta pentru Copii ?Louis Turcanu? /ID# 235608

Timișoara, Timiș County, Romania

Spitalul Clinic de Boli infectioase si Tropicale Dr. Victor Babes /ID# 235610

Bucharest, , Romania

Spitalul Clinic Judeatean Mures /ID# 234728

Târgu Mureş, , Romania

Smolensk State Medical University /ID# 236996

Smolensk, , Russia

Stavropol State Medical University /ID# 236239

Stavropol, , Russia

Regional Childrens Hospital /ID# 235560

Vologda, , Russia

Peermed Clinical Trial Centre /ID# 235514

Kempton Park, Gauteng, South Africa

Mzansi Ethical Research Center /ID# 236480

Middelburg, Mpumalanga, South Africa

Complejo Hospitalario Universitario de Santiago /ID# 235512

Santiago de Compostela, A Coruna, Spain

Hospital Sant Joan de Deu /ID# 236797

Esplugues de Llobregat, Barcelona, Spain

Hospital Donostia /ID# 237773

Donostia / San Sebastian, Guipuzcoa, Spain

Hospital General Universitario Gregorio Maranon /ID# 236955

Madrid, , Spain

Hospital Universitario La Paz /ID# 237775

Madrid, , Spain

Hospital Universitario y Politecnico La Fe /ID# 237086

Valencia, , Spain

Ivano-Frankivsk Pediatric Regional Clinical Hospital /ID# 235556

Ivano-Frankivsk, Ivano-Frankivsk Oblast, Ukraine

Dnipropetrovsk Regional children's Clinical Hospital /ID# 235558

Dnipro, , Ukraine

PE PMC Acinus, Medical and Diagnostic Center /ID# 237514

Kropyvnytskyi, , Ukraine

Lviv Regional Clinical Hospital /ID# 236921

Lviv, , Ukraine

Ukrainian Medical Stomatological Academy - Children's City Clinical Hospital /ID# 234886

Poltava, , Ukraine

Communal Nonprofit Enterprise "Central City Clinical Hospital" of Uzhhorod City /ID# 238058

Uzhhorod, , Ukraine

Countries

United States; Argentina; Belarus; Brazil; Bulgaria; Chile; Colombia; Georgia; Greece; Guatemala; Latvia; Lithuania; Mexico; Panama; Poland; Romania; Russia; South Africa; Spain; Ukraine

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.rxabbvie.com/

Related info

Other Identifiers

2014-005281-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

DUR001-306

Identifier Type: -

Identifier Source: org_study_id