A Prospective, Multicenter, Double-Blind, Randomized, Comparative Study to Evaluale the Safety, Tolerabílity, and Efficacy of MK-0826 Versus Piperacillin/Tazobactam in the Treatment of Complicated Skin and Skin Structure Infections inAdults

Not Applicable

• Conditions: -L089 Local infection of skin and subcutaneous tissue, unspecified; Local infection of skin and subcutaneous tissue, unspecified; L089

• Registration Number: PER-029-99
• Lead Sponsor: MERCK SHARP & DOHME PERÚ S.R.L.,

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 1998-06-11
• Last Update Posted: 4 September 2023

Recruitment & Eligibility

• Status: Complete
• Sex: Not specified
• Target Recruitment: 0

Inclusion Criteria

a. Adult patients (age >18 years) wiih a clinically and/or bacteriologically documented complicated skin or skin structure (soft tissue) infection judged by the investigator to be serious (requiring parenteral antibiotic therapy) and treatable within a 14-day therapeutic period.
b. For a clinical diagnosis of complicated skin or skin structure infection. patients must have well-documented signs and symptoms of acute infection (present for <1 days) in the absence of a chronic skin disease (e.g., eczema, atopic dermatitis), or an associated indwelling foreign material (such as a central venous catheter, peripheral intravenous line, or pacemaker). These
should include either;
1) purulent drainage or collection from the wound or lesion
OR
2) At least three of the following;
a) Fever. defined as maximal body temperature measurements >37.8°C (100°F) orally, >38.2°C (100.8°F) by tympanic measurement, or >38.4°C (101.0°F) by rectal measurement within the 24 hours prior to enrollment
b) WBC >10,0(X) with >5% immature neutrophils (bands)
c) Local erythema extending >1 cm away from the wound edge or abscess cavity
d) Localized swelling
e) Localized tendemess or pain
f) Localized fluctuance
g) Lymphangitis associated with a skin lesión
h) Localized warmth
i) Localized induration
c. Patients with either of the following two broad classifications of complicated skin and skin structure infections should be included in this study:
1) Infections in patients with complicating underlying disease states such as:
a) Lower extremity infections (defined as at least the presence of cellulitis with or without ulceration or purulent discharge) in a patient with insulin-dependent diabetes mellitus or neuropathy.
b) Acutely infected pressure ulcers. Ulcers in these patients should be no greater than 14 days in duration and without underlying osteomyelitis. Infection should represent a significant acute change.
2) All other complicated skin and skin structure infections including:
a) Perineal abscesses, cellulitis or deep tissue infectíon where anaerobes or Enterobacteriaceae are likely to play a role.
b) Infections of traumatic or surgical wound sites.
c) Deep skin structure or soft tissue infections developing in the absence of identifiable injury.
d) Extensive abscesses and infections of deeper soft tissues which require significant surgical incision and drainage as well as antimicrobial therapy.
e) Areas of extensive cellulitis (greater than 10 cm) and complicated by purulent drainage (demonstrated as polymorphonuclear leukocytes and bacteria on gram stain) or purulent fluid collection.
d. All patients must have an appropriately obtained wound culture sent within 48 hours prior to the start of therapy.
• Patients with negative admission cultures should stíll remain in the study for ciinical effícacy evaluation.
• Superficial surface cultures are not acceptable.
• Patients with ulcers secondary to diabetes mellitus, neuropathy, or other causes must have the wound sterilely debrided of devitalized tissue prior to the enrollment culture which should be obtained from the base of the wound, from loculated pus.
e. Patients with multiple sites of infection may be enrolled.
f. females of childbearing potential must have a negative serum pregnancy test (b-HCG) prior to enrollment into the study and subsequently use

Exclusion Criteria

a. Patients with the following infections should be excluded from this studY:
1) Uncomplicated skin infections: such as simple abscesses requiring only needle aspiration, or surgical drainage but not parenteral antimicrobial therapy, impetigo, furunculosis, carbunculosis, cellulitis (other than perineal), or folliculitis in normal hosts.
2) Skin infections known at admission to be caused by pathogens resistant to either of the study drugs.
3) Infected bum wounds.
4) Patients with necrotizing fasciitis.
5) Concurrent infections that would interfere with the evaluation of response to the study antibiotic.
6) Patients having evidence of osteomyelitis or septic arthritis contiguous with the skin or skin structure infection.
If clinically suspected, osteomyelitis should be determined by clinical assessment and by at least one of the following: X ray, magnetic resonance imaging, bone culture/pathology, technetium bone scanning, indium-labeled white blood cell scanning.
7) Infections of prosthetic materials.
b. Failure to meet all of the inclusion criteria.
c. Rapidly progressive or terminal illness; patients in whom a response to 7 to 14 days of antibiotic therapy is considered unlikely, or patients who are considered unlikely to survive the study period.
d. Patients whose wound contains concomitant gangrene or who are likely, in the opinion of the investigator, to require amputation of the infected area.
e. Patients with deep venous thrombosis.
f. Immunodeficient patients such as HIV seropositive patients with a clinical diagnosis of AIDS or patients whose absolute neutrophil count (ANC) is <500 cells/mm^.
g. Patients treated with >24 hours of systemic antibiotic therapy known to be effective against the presumed or documented etiologic pathogen(s) within the 72-hour period inmediately prior to consideration for entry into the study (except if the admission culture shows persistence of a pathogen).
h. History of serious allergy, hypersensitivity (e.g., anaphylaxis), or any serious reaction to carbapenem antibiotics (such as imipenem), piperacillin/
tazobactam, any penicillins, or other P-lactam agents. Patients with history of mild rash to penicillins or other p-lactants may be enrolled.
i. The need for concomitant systemic antibacterials in addition to those designated in the 2 study groups.
j. The presence of azotemia as defined by serum creatinine >1.5X the upper limit of the range of normal values used by the laboratory performing the test for patients <65 years of age. and >1.25X the upper limit of the range of normal values used by the laboratory performing the test for patients >65 years of age.
NOTE: For patients with volume depletion and elevated creatinine, this test can be repeated after volume replacement during the screening period. If the serum creatinine value is within the specified limits before study entry, the patient will be eligible. When data from a clinical study of pharmacokinetics of MK-0826 in renal failure become available, it will be possible to enroll patients with renal insufficiency, provided they do not require dialysis, with adjustment of dose as necessary.
k. Pregnant women, nursing women, or fertile women not practicing adequate methods of contraception; women planning to become pregnant within 1 month of the study.
1. Participation in any other clinical study involving the administration of medica

Study & Design

• Study Type: Interventional
• Study Design: Not specified