Study Evaluating Safety and Efficacy of Tigecycline Versus Imipenem/Cilastatin Subjects With Hospital-Acquired Pneumonia

NCT00707239 | Terminated Phase 2 Results DMC

• 2 other identifiers: 3074K6-2000B1811004
• Study Type: interventional
• Target: 108
• Locations: 14 countries
• Sites: 40

Brief Summary

This study will compare the safety and efficacy of a tigecycline regimen versus an imipenem/cilastatin regimen for the treatment of subjects who are hospitalized with hospital-acquired pneumonia (HAP). At least 70% of enrolled subjects will have ventilator-associated pneumonia (VAP). Two dose levels of tigecycline will be assessed and compared to imipenem/cilastatin in parallel. Subjects will receive intravenous therapy from a minimum of 7 \& up to 14 consecutive days, the exact duration will be at the decision of the investigator based on the subject's condition. Additional protocol specified antibiotics may be given to ensure appropriate coverage. A final assessment at test-of-cure (TOC) visit will be done 10 to 21 days after the last day of therapy. The total duration of subject participation will be between 17 and 44 days, including a follow up period of 30 days after the last day of therapy for SAEs. Subjects will be followed for safety and efficacy. The safety assessment will include: physical examinations, vital signs, assessment of the clinical signs and symptoms of pneumonia, collection of adverse events, 12-lead ECG, collection of samples for hematology, serum chemistries, and coagulation parameters, \& a serum or urine pregnancy test before study entry for women of childbearing potential. The clinical and microbiological efficacy will both be evaluated.

Conditions

Pneumonia, Bacterial

Keywords

Hospital-acquired pneumonia; Ventilator-associated pneumonia

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Clinical Response in Clinically Evaluable (CE) Population at Test-of-Cure (TOC) Visit

  Clinical response: Cure=All initial signs/symptoms of pneumonia (SSx) improved; chest x-ray (CXR) improved/stable; no other antibiotics for pneumonia; no worsening or new SSx. Failure=Persistence or worsening SSx; no clinical improvement or initial improvement with clinically important worsening; other antimicrobials for pneumonia; CXR progression; death \> study day 2 due to pneumonia. Indeterminate=unable to determine outcome for non-study drug/infection reasons (e.g., lost to follow-up); death in 2 days after 1st dose for any reason, or \>2 days but before TOC visit for non-pneumonia reason.

  Up to Day 24 to 35 (10 to 21 days after last day of therapy [LDOT])

Secondary Outcomes (4)

• Percentage of Participants With Clinical Response in Clinical Modified Intent-to-treat (c-mITT) Population at Test-of-Cure (TOC) Visit

  Up to Day 24 to 35 (10 to 21 days after LDOT)

• Percentage of Participants With Clinical Response in Ventilator Associated Pneumonia (VAP) and Non-VAP Participants at Test-of-Cure (TOC) Visit

  Up to Day 24 to 35 (10 to 21 days after LDOT)

• Percentage of Participants With Microbiological Response at the Pathogen Level Population at Test-of-Cure (TOC) Visit

  Up to Day 24 to 35 (10 to 21 days after LDOT)

• Percentage of Participants With Microbiological Response at the Participant Level Population at Test-of-Cure (TOC) Visit

  Up to Day 24 to 35 (10 to 21 days after LDOT)

Other Outcomes (14)

• Number of Participants Who Experienced Nausea or Vomiting

  Baseline up to Day 29 to Day 35 (15 to 21 days after LDOT)

• Number of Participants With Abnormal Laboratory Examinations

  Baseline up to Day 24 to Day 35 (10 to 21 days after LDOT)

• Number of Participants With Abnormal Electrocardiogram (ECG)

  Baseline up to Day 14 or LDOT

Study Arms (3)

A

EXPERIMENTAL

Drug: tigecycline

B

EXPERIMENTAL

Drug: tigecycline

C

ACTIVE COMPARATOR

Drug: imipenem/cilastatin

Interventions

tigecycline DRUG

An initial intravenous (IV) loading dose of 150 mg of tigecycline, followed by 75 mg of IV tigecycline approximately every 12 hours (q12h), for up to 14 consecutive days. Ceftazidime 2 g IV approximately every 8 hours, an aminoglycoside (tobramycin 7mg/kg daily or amikacin 20 mg/kg daily) and vancomycin placebo given at the start of therapy (unless it is known at baseline that the subject does not have Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus \[MRSA\]).

A

imipenem/cilastatin DRUG

Imipenem/cilastatin 1g intravenous (IV) will be administered approximately every 8 hours, for up to 14 consecutive days. In addition vancomycin 15 mg/kg IV approximately every 12 hours (q12h), an aminoglycoside (tobramycin 7mg/kg daily or amikacin 20 mg/kg daily) and ceftazidime placebo will be given at the start of therapy (unless it is known at baseline that the subject does not have Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus \[MRSA\]).

C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects, greater than or equal to 18 years of age, known or suspected to have acute hospital-acquired pneumonia (HAP).
• Acute HAP is defined as pneumonia with onset of symptoms:
• Greater than or equal to 48 hours after admission to an acute care hospital or chronic care facility such as a skilled nursing home facility or rehabilitation unit. Or
• Less than or equal to 7 days after the subject was discharged from the hospital. The initial hospitalization must have been greater than or equal to 3 days duration.
• VAP is defined as: onset of symptoms of pneumonia greater than or equal to 48 hours after endotracheal intubation.
• Presence of a new or evolving infiltrate on a chest x-ray film, presence of fever or leukocytosis, respiratory failure requiring mechanical ventilation or presence of 2 of the following clinical signs and symptoms: cough, dyspnea or tachypnea, pleuritic chest pain, rales and/or evidence of pulmonary consolidation, hypoxemia, or purulent sputum production.

You may not qualify if:

• Subjects with other significant underlying conditions that would make it difficult to evaluate the subjects or make it unlikely to complete the therapy or that would increase their risk by participating in the study, infection with organisms known to be resistant, contraindication, or hypersensitivity to any of the test articles.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (40)

Pfizer Investigational Site

Louisville, Kentucky, United States

Location

Pfizer Investigational Site

Omaha, Nebraska, 68131, United States

Location

Pfizer Investigational Site

Morgantown, West Virginia, 26506, United States

Location

Pfizer Investigational Site

La Plata, Buenos Aires, 1900, Argentina

Location

Pfizer Investigational Site

La Plata, Buenos Aires, B1900AVG, Argentina

Location

Pfizer Investigational Site

Godoy Cruz, Mendoza Province, Argentina

Location

Pfizer Investigational Site

Provincia de Buenos Aires, Argentina

Location

Pfizer Investigational Site

Nambour, Queensland, 4560, Australia

Location

Pfizer Investigational Site

Victoria, Victoria, 3128, Australia

Location

Pfizer Investigational Site

Belo Horizonte, Minas Gerais, 30150-221, Brazil

Location

Pfizer Investigational Site

Porto Alegre, Rio Grande do Sul, 90610-000, Brazil

Location

Pfizer Investigational Site

São José do Rio Preto, São Paulo, 15090-000, Brazil

Location

Pfizer Investigational Site

Chicoutimi, Quebec, G7H 5H6, Canada

Location

Pfizer Investigational Site

Trois-Rivières, Quebec, G8Z 3R9, Canada

Location

Pfizer Investigational Site

Santiago, Santiago Metropolitan, Chile

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Pfizer Investigational Site

Medellín, Antioquia, Colombia

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Pfizer Investigational Site

Bogotá, Colombia

Location

Pfizer Investigational Site

Zagreb, 10000, Croatia

Location

Pfizer Investigational Site

Argenteuil, 95100, France

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Pfizer Investigational Site

Debrecen, 4043, Hungary

Location

Pfizer Investigational Site

Nyíregyháza, 4400, Hungary

Location

Pfizer Investigational Site

Székesfehérvár, 8000, Hungary

Location

Pfizer Investigational Site

Vác, 2600, Hungary

Location

Pfizer Investigational Site

Daugavpils, LV-5417, Latvia

Location

Pfizer Investigational Site

Riga, 1001, Latvia

Location

Pfizer Investigational Site

Riga, LV-1001, Latvia

Location

Pfizer Investigational Site

Moscow, 119620, Russia

Location

Pfizer Investigational Site

Moscow, 121359, Russia

Location

Pfizer Investigational Site

Novosibirsk, 630051, Russia

Location

Pfizer Investigational Site

Saint Petersburg, 194354, Russia

Location

Pfizer Investigational Site

Saint Petersburg, 196247, Russia

Location

Pfizer Investigational Site

Vsevolozhsk, 188640, Russia

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Pfizer Investigational Site

Seoul, Korea, 135 710, South Korea

Location

Pfizer Investigational Site

Seoul, Korea, 136-705, South Korea

Location

Pfizer Investigational Site

Seoul, Korea, 138-736, South Korea

Location

Pfizer Investigational Site

Seoul, Korea, 152-703, South Korea

Location

Pfizer Investigational Site

Tainan, Taiwan, 407, Taiwan

Location

Pfizer Investigational Site

Taipei, Taiwan, 100, Taiwan

Location

Pfizer Investigational Site

Tainan, Taiwan

Location

Pfizer Investigational Site

Taipei TOC, 100, Taiwan

Location

Related Publications (1)

• Ramirez J, Dartois N, Gandjini H, Yan JL, Korth-Bradley J, McGovern PC. Randomized phase 2 trial to evaluate the clinical efficacy of two high-dosage tigecycline regimens versus imipenem-cilastatin for treatment of hospital-acquired pneumonia. Antimicrob Agents Chemother. 2013 Apr;57(4):1756-62. doi: 10.1128/AAC.01232-12. Epub 2013 Jan 28.

  PMID: 23357775 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Pneumonia, Bacterial; Healthcare-Associated Pneumonia; Pneumonia, Ventilator-Associated

Interventions

Tigecycline; Cilastatin, Imipenem Drug Combination

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Cross Infection; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Imipenem; Thienamycins; Carbapenems; beta-Lactams; Lactams; Amides; Cilastatin; Cyclopropanes; Cycloparaffins; Hydrocarbons, Alicyclic; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Fatty Acids; Lipids; Drug Combinations; Pharmaceutical Preparations

Limitations and Caveats

Formal statistical conclusions could not be made due to premature termination of study, because of enrollment difficulties, and small number of enrolled participants.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2008
• First Posted: June 30, 2008
• Study Start: December 1, 2008
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2011
• Last Updated: July 10, 2012
• Results First Posted: July 10, 2012

Record last verified: 2012-06

Locations

CL (1); FR (1); CO (2); BR (3); AR (4); AU (2); CR (1); RU (6); CA (2); US (3); KR (4); TW (4); LA (3); HU (4)