Trial to Evaluate Beta-Lactam Antimicrobial Therapy of Community Acquired Pneumonia in Children

NCT02891915 | Completed Phase 4 Results FDA Drug

• 2 other identifiers: 14-0079HHSN272201300023I
• Study Type: interventional
• Target: 385
• Locations: 1 country
• Sites: 9

Brief Summary

This is a multi-center, randomized, double-blind, placebo-controlled, superiority clinical trial will test the effectiveness of short (5-day) vs.standard (10-day) course therapy in children who are diagnosed with CAP and initially treated in outpatient clinics, urgent care facilities, and emergency departments. Primary objective is to compare the composite overall outcome (Desirability of Outcome Ranking, DOOR) among children 6-71 months of age with CAP assigned to a strategy of short course (5 days) vs standard course (10 days) outpatient beta-lactam therapy at Outcome Assessment Visit #1 (Study Day 8 +/- 2 days)

Conditions

Pneumonia

Keywords

Antimicrobial; Beta-Lactam; Pneumonia; Short Course; Standard Course; Therapy

Outcome Measures

Primary Outcomes (1)

• Desirability of Outcome Ranking (DOOR)

  DOOR is a composite endpoint created using clinical outcomes from the first 5 days and at Outcome Assessment Visit #1 (OAV #1). It is based on adequate clinical response at OAV #1, solicited symptoms from first 5 days and number of days of antibiotics use for worsening pneumonia from the first 5 days of the study.

  Outcome Assessment Visit 1 (Study Day 8 +/- 2 days)

Secondary Outcomes (11)

• Desirability of Outcome Ranking (DOOR)

  Outcome Assessment Visit 2 (Study Day 22 +/- 3 days)

• Resolution of Symptoms (a Component of DOOR)

  Outcome Assessment Visit 1 (Study Day 8 +/- 2 days)

• Resolution of Symptoms (a Component of DOOR)

  Outcome Assessment Visit 2 (Study Day 22 +/- 3 days)

• Adequate Clinical Response Rates (a Component of DOOR)

  Outcome Assessment Visit 1 (Study Day 8 +/- 2 days)

• Adequate Clinical Response Rates (a Component of DOOR)

  Outcome Assessment Visit 2 (Study Day 22 +/- 3 days)

Study Arms (2)

Short

ACTIVE COMPARATOR

200 subjects will receive a short course of the initially prescribed antibiotic for 5 days plus 5 days of matching placebo

Drug: Amoxicillin; Drug: Amoxicillin-clavulanate; Drug: Cefdinir; Other: Placebo

Standard

ACTIVE COMPARATOR

200 subjects will receive a standard course of the initially prescribed antibiotic( Amoxicillin, Amoxicillin-Clavulanate, Cefdinir) for 10 days

Drug: Amoxicillin; Drug: Amoxicillin-clavulanate; Drug: Cefdinir

Interventions

Amoxicillin DRUG

Amoxicillin is an aminopenicillin antibiotic

Short; Standard

Amoxicillin-clavulanate DRUG

A fixed-ratio combination of amoxicillin trihydrate, an aminopenicillin, and potassium clavulanate, a beta-lactamase inhibitor, used to treat a broad-spectrum of bacterial infections, especially resistant strains.

Short; Standard

Cefdinir DRUG

Cefdinir is a cephalosporin antibiotic used to treat bacterial infections in many different parts of the body.

Short; Standard

Placebo OTHER

Placebo

Short

Eligibility Criteria

• Age: 6 Months - 71 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age 6 - 71 months
• Provider diagnosis of CAP and prescription of antibiotic therapy with amoxicillin, amoxicillin-clavulanate, or cefdinir
• \- amoxicillin or amoxicillin-clavulanate prescribed at a amoxicillin dose of 60 mg/kg/day
• \-- cefdinir prescribed at a minimum dose of 10 mg/kg/day
• Parental report of clinical improvement
• \- based on lack of either subjective or known fever temperature \>/= 38.3°C in the preceding 24 hours; current respiratory rate no greater than 50 breaths/minute (\<2 years of age) or breaths/minute (= / \> 2 years of age); and current grade of cough \< 3
• Ability of a parent or guardian to understand and comply with the study procedures and be available for all study visits
• Signed written informed consent by a parent or guardian

You may not qualify if:

• \. Treatment with any systemic antibiotic therapy within 7 days before the diagnosis of CAP 2. Initial therapy for CAP with combination antibiotic therapy
• amoxicillin, amoxicillin/clavulanate or cefdinir plus one or more additional oral, intravenous, or intramuscular antibiotics 3. History of anaphylaxis or severe drug allergy to amoxicillin, if prescribed amoxicillin or amoxicillin/clavulanic acid; or oral cephalosporin antibiotics (except cefaclor), if prescribed cefdinir 4. Presence of concomitant bacterial infection that requires \> 5 days of antibiotic therapy 5. Radiographic findings (where applicable) of complicated pneumonia at presentation or any subsequent chest radiograph up to the time of enrollment
• clinically significant pleural effusion, lung abscess, or pneumatocele 6. Hospitalization for pneumonia during Day -5 to -1 of antibiotic therapy for CAP
• persistent asthma is defined as receiving daily asthma maintenance therapy such as inhaled corticosteroids, cromolyn, theophylline, or leukotriene receptor antagonists
• \-- acute asthma exacerbation is defined as receiving concomitant bronchodilator therapy and systemic corticosteroids 10. Provider-diagnosis of aspiration pneumonia, bronchiolitis, or bronchitis 11. Surgery or other invasive procedures of the upper or lower airway (e.g., bronchoscopy, laryngoscopy) with general anesthesia or hospitalization \</=7 days before diagnosis of CAP 12. History of an underlying chronic medical condition
• HIV infection, primary immunodeficiency, anatomic or functional asplenia; receipt of a hematopoietic stem cell or solid organ transplant at any time; receipt of immunosuppressive therapy including chemotherapeutic agents, biologic agents, antimetabolites or radiation therapy during the past 12 months; or daily use of systemic corticosteroids for more than 7 consecutive days during the past 14 days 14. Any other condition that in the judgment of the investigator precludes participation because it could affect the safety of the subject 15. Current enrollment in another clinical trial of an investigational agent 16. Previous enrollment in this trial

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (9)

University of Alabama - Children's of Alabama - Infectious Diseases/Virology

Birmingham, Alabama, 35233-1711, United States

Location

Arkansas Children's Hospital - Infectious Diseases

Little Rock, Arkansas, 72202-3500, United States

Location

University of Louisville School of Medicine - Norton Children's Hospital - Infectious Diseases

Louisville, Kentucky, 40202, United States

Location

Washington University School of Medicine in St. Louis - Infectious Diseases

St Louis, Missouri, 63110-1010, United States

Location

Duke Human Vaccine Institute - Duke Vaccine and Trials Unit

Durham, North Carolina, 27704, United States

Location

Cincinnati Children's Hospital Medical Center - Infectious Diseases

Cincinnati, Ohio, 45229-3039, United States

Location

Children's Hospital of Philadelphia - The Center for Pediatric Clinical Effectiveness

Philadelphia, Pennsylvania, 19104-3309, United States

Location

Children's Hospital of Pittsburgh of UPMC - General Academic Pediatric

Pittsburgh, Pennsylvania, 15213-3205, United States

Location

Vanderbilt University - Pediatric - Vanderbilt Vaccine Research Center

Nashville, Tennessee, 37232-2573, United States

Location

Related Publications (2)

• Pettigrew MM, Kwon J, Gent JF, Kong Y, Wade M, Williams DJ, Creech CB, Evans S, Pan Q, Walter EB, Martin JM, Gerber JS, Newland JG, Hofto ME, Staat MA, Fowler VG, Chambers HF, Huskins WC; Antibacterial Resistance Leadership Group. Comparison of the Respiratory Resistomes and Microbiota in Children Receiving Short versus Standard Course Treatment for Community-Acquired Pneumonia. mBio. 2022 Apr 26;13(2):e0019522. doi: 10.1128/mbio.00195-22. Epub 2022 Mar 24.

  PMID: 35323040 DERIVED

• Williams DJ, Creech CB, Walter EB, Martin JM, Gerber JS, Newland JG, Howard L, Hofto ME, Staat MA, Oler RE, Tuyishimire B, Conrad TM, Lee MS, Ghazaryan V, Pettigrew MM, Fowler VG Jr, Chambers HF, Zaoutis TE, Evans S, Huskins WC; The DMID 14-0079 Study Team. Short- vs Standard-Course Outpatient Antibiotic Therapy for Community-Acquired Pneumonia in Children: The SCOUT-CAP Randomized Clinical Trial. JAMA Pediatr. 2022 Mar 1;176(3):253-261. doi: 10.1001/jamapediatrics.2021.5547.

  PMID: 35040920 DERIVED

MeSH Terms

Conditions

Pneumonia

Interventions

Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Cefdinir

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Ampicillin; Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Clavulanic Acid; Clavulanic Acids; Drug Combinations; Pharmaceutical Preparations; Cephalosporins; Thiazines

Results Point of Contact

• Title: Dr. C. Buddy Creech
• Organization: Vanderbilt Vaccine Research Program

buddy.creech@vanderbilt.edu

615-343-0332

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2016
• First Posted: September 8, 2016
• Study Start: December 2, 2016
• Primary Completion: December 16, 2019
• Study Completion: December 16, 2019
• Last Updated: February 3, 2021
• Results First Posted: February 3, 2021

Record last verified: 2017-04-05

Locations

US (9)