Clinical trial NCT02127970: Single Dose vs. Two Dose Regimen of Dalbavancin for the Treatment of Acute Bacterial Skin and Skin Structure Infections
Official title: A Phase 3b, Double-Blind, Multicenter, Randomized Study to Compare the Efficacy and Safety of Single Dose Dalbavancin to a Two Dose Regimen of Dalbavancin for the Treatment of Acute Bacterial Skin and Skin Structure Infections
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Abscess
Wound Infection
Surgical Site Infection
Cellulitis
Lead sponsor: Durata Therapeutics Inc., an affiliate of Allergan plc
Sponsor class: INDUSTRY
First posted: 2014-05-01
Enrollment: 698
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To compare the efficacy of treatment with a single dose of dalbavancin 1500 mg to treatment with a two dose regimen of dalbavancin (1000 mg on Day 1 followed by 500 mg on Day 8) in participants with known or suspected Gram-positive acute bacterial skin and skin structure infections (ABSSSI) at 48 -72 hours after initiation of treatment.


Eligibility criteria: Inclusion Criteria:

* Male or female participants 18 - 85 years of age.
* Signed and dated informed consent document.
* Major abscess, surgical site infection, traumatic wound infection or cellulitis suspected or confirmed to be caused by Gram-positive bacteria.
* At least two (2) local signs and symptoms of acute bacterial skin and skin structure infection (ABSSSI and at least one systemic sign of infection.
* Participant willing and able to comply with study procedures.

Exclusion Criteria:

* A contra-indication to dalbavancin.
* Pregnant or nursing females.
* Sustained shock.
* Participation in another study of an investigational drug or device within 30 days.
* Receipt of a systemically or topically administered antibiotic with a Gram-positive spectrum that achieves therapeutic concentrations in the serum or at the site of the ABSSSI within 14 days prior to randomization. An exception is allowed for participants receiving a single dose of a short-acting (half-life ≤ 12 hours) antibacterial drug prior to randomization; up to 25% of participants may have received such therapy.
* Infection due to an organism known prior to study entry to be resistant to dalbavancin or vancomycin (vancomycin MIC (minimum inhibitory concentration) \>8 μg/mL).
* Evidence of meningitis, necrotizing fasciitis, gas gangrene, gangrene, septic arthritis, osteomyelitis; endovascular infection, such as clinical and/or echocardiographic evidence of endocarditis or septic thrombophlebitis.
* 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.
* Venous catheter entry site infection.
* Infections involving a diabetic foot ulceration, perirectal abscess or a decubitus ulcer.
* Participant 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, hemodialysis catheter, implantable pacemaker or defibrillator, intra-aortic balloon pump, left ventricular assist device, a peritoneal dialysis catheter, or a neurosurgical device such as a ventricular peritoneal shunt, intra-cranial pressure monitor, or epidural catheter.
* 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 participant should be removed from study treatment and receive appropriate antibiotic(s) to treat the Gram-negative bacteremia. Such participants must have an end of treatment (EOT) visit performed within 3 calendar days after discontinuing study medication but are required to have AEs (adverse events) reported through the Final Visit.
* Participants whose ABSSSI is the result of having sustained full or partial thickness burns.
* Participants with an infection involving a limb with evidence of critical ischemia of an affected limb defined as any of the following criteria: absent or abnormal Doppler wave forms, toe blood pressure of \<45 mm Hg, ankle brachial index \<0.5, and/ or critical ischemia as assessed by a vascular surgeon.
* Participants with ABSSSI such as superficial/simple cellulitis/erysipelas, impetiginous lesion, furuncle, or simple abscess that only requires surgical drainage for cure.
* Concomitant condition requiring any antibiotic therapy that would interfere with the assessment of study drug for the condition under study.
* Anticipated need of antibiotic therapy for longer than 14 days.
* Participants who are placed in a hyperbaric chamber as adjunctive therapy for the ABSSSI.
* More than 2 surgical interventions (defined as procedures conducted under sterile technique and typically unable to be performed at the bedside) for the ABSSSI, or participants who are expected to require more than 2 such interventions.
* 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).
* Absolute neutrophil count \<500 cells/mm\^3.
* Known or suspected human immunodeficiency virus (HIV) infected participants with a CD4 (cluster of differentiation 4) cell count \<200 cells/mm3 or with a past or current acquired immunodeficiency syndrome (AIDS)-defining condition and unknown CD4 count.
* Participants with a recent bone marrow transplant (in post-transplant hospital stay).
* Participants receiving oral steroids \>20 mg prednisolone per day (or equivalent) or receiving immunosuppressant drugs after organ transplantation.
* Participants with a rapidly fatal illness, who are not expected to survive for 3 months.
* Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participants inappropriate for entry into this study.
* Prior participation in this study.

Primary outcomes:
measure: Percentage of Participants Who Were Clinical Responders 48-72 Hours After the Initiation of Study Drug
timeFrame: Up to 48-72 hours after the initiation of study drug
Secondary outcomes:
measure: Percentage of Participants by Clinical Status at End of Treatment (EOT) and Final Visit (FV)
timeFrame: End of Treatment (Day 14-15 after the initiation of study drug) and Final Visit (28 ±2 days after the initiation of study drug)
Other outcomes:
measure: Percentage of Participants by Clinical Status Based on Localized Fluctuance and Heat/Warmth at End of Treatment (EOT)
timeFrame: EOT (Day 14-15)
measure: Percentage of Participants by Investigator Assessment of Clinical Outcome
timeFrame: Day 3-4, Day 8, EOT (Day 14-15) and Final Visit (Day 28 +/- 2 days)
measure: Percentage of Participants Achieving Clinical Outcome of Success Based on Key Target Pathogen at Baseline
timeFrame: Day 3-4 and EOT (Day 14-15)
measure: Percentage of Participants With Complete Resolution of Local Signs of Infection
timeFrame: Day 3-4, Day 8, EOT (Day 14-15) and Final Visit (Day 28 +/- 2 days)
measure: Change From Baseline in Participant's Assessment of Pain
timeFrame: Baseline (Day 0) to Day 3-4, Day 8, EOT (Day 14-15) and Final Visit (Day 28 + /- 2 days)
measure: Percentage of Participants by Resource Utilization Categories
timeFrame: Final Visit (Day 28 +/- 2 days)
measure: Percentage of Participants by Skin and Soft Tissue Infection-Convenience (SSTI-C) Questionnaire: Overall Satisfaction Response
timeFrame: EOT (Day 14-15)
Locations:
city: Montgomery
country: United States
facility: 110
state: Alabama
city: Anaheim
country: United States
facility: 103
state: California
city: Long Beach
country: United States
facility: 117
state: California
city: Long Beach
country: United States
facility: 106
state: California
city: Modesto
country: United States
facility: 118
state: California
city: San Diego
country: United States
facility: 104
state: California
city: San Diego
country: United States
facility: 113
state: California
city: San Diego
country: United States
facility: 115
state: California
city: San Diego
country: United States
facility: 116
state: California
city: Stockton
country: United States
facility: 108
state: California
city: Sylmar
country: United States
facility: 105
state: California
city: Washington
country: United States
facility: 112
state: District of Columbia
city: Orlando
country: United States
facility: 107
state: Florida
city: Saint Cloud
country: United States
facility: 120
state: Florida
city: Augusta
country: United States
facility: 114
state: Georgia
city: Columbus
country: United States
facility: 122
state: Georgia
city: Savannah
country: United States
facility: 125
state: Georgia
city: Eunice
country: United States
facility: 119
state: Louisiana
city: Springfield
country: United States
facility: 101
state: Massachusetts
city: Detroit
country: United States
facility: 109
state: Michigan
city: Butte
country: United States
facility: 121
state: Montana
city: Omaha
country: United States
facility: 123
state: Nebraska
city: Toledo
country: United States
facility: 111
state: Ohio
city: Franklin
country: United States
facility: 126
state: Tennessee
city: Smyrna
country: United States
facility: 127
state: Tennessee
city: Sofia
country: Bulgaria
facility: 802
city: Sofia
country: Bulgaria
facility: 800
city: Sofia
country: Bulgaria
facility: 801
city: Zagreb
country: Croatia
facility: 200
city: Zagreb
country: Croatia
facility: 201
city: Tallinn
country: Estonia
facility: 253
city: Tallinn
country: Estonia
facility: 252
city: Tartu
country: Estonia
facility: 251
city: Kutaisi
country: Georgia
facility: 302
city: Tbilisi
country: Georgia
facility: 303
city: Tbilisi
country: Georgia
facility: 300
city: Tbilisi
country: Georgia
facility: 301
city: Debrecen
country: Hungary
facility: 352
city: Kaposvar
country: Hungary
facility: 353
city: Pecs
country: Hungary
facility: 354
city: Szeged
country: Hungary
facility: 351
city: Daugavpils
country: Latvia
facility: 402
city: Liepaja
country: Latvia
facility: 401
city: Rezekne
country: Latvia
facility: 403
city: Riga
country: Latvia
facility: 400
city: Riga
country: Latvia
facility: 404
city: Cluj-Napoca
country: Romania
facility: 501
state: Cluj County
city: Bucharest
country: Romania
facility: 502
city: Bucharest
country: Romania
facility: 500
city: Bucharest
country: Romania
facility: 503
city: Vsevolozhsk
country: Russian Federation
facility: 555
state: Leningrad Region
city: Irkutsk
country: Russian Federation
facility: 557
city: Moscow
country: Russian Federation
facility: 552
city: Moscow
country: Russian Federation
facility: 554
city: Novosibirsk
country: Russian Federation
facility: 553
city: St. Petersburg
country: Russian Federation
facility: 551
city: Tomsk
country: Russian Federation
facility: 556
city: Belgrade
country: Serbia
facility: 600
city: Belgrade
country: Serbia
facility: 601
city: Nis
country: Serbia
facility: 603
city: Novi Sad
country: Serbia
facility: 602
city: Breyten
country: South Africa
facility: 756
city: Cape Town
country: South Africa
facility: 760
city: Dundee
country: South Africa
facility: 752
city: Johannesburg
country: South Africa
facility: 755
city: Middleburg
country: South Africa
facility: 751
city: Port Elizabeth
country: South Africa
facility: 758
city: Pretoria
country: South Africa
facility: 757
city: Pretoria
country: South Africa
facility: 753
city: Pretoria
country: South Africa
facility: 759
city: Worcester
country: South Africa
facility: 754
city: Cherkasy
country: Ukraine
facility: 700
city: Dnipropetrovsk
country: Ukraine
facility: 704
city: Ivano-Frankivsk
country: Ukraine
facility: 706
city: Ivano-Frankivsk
country: Ukraine
facility: 701
city: Kharkiv
country: Ukraine
facility: 705
city: Lviv
country: Ukraine
facility: 703
city: Zaporizhzhya
country: Ukraine
facility: 702
Study officials:
affiliation: Allergan
name: Urania Rappo, MD
role: STUDY_DIRECTOR
References:
citation: Gonzalez PL, Rappo U, Akinapelli K, McGregor JS, Puttagunta S, Dunne MW. Outcomes in Patients with Staphylococcus aureus Bacteremia Treated with Dalbavancin in Clinical Trials. Infect Dis Ther. 2022 Feb;11(1):423-434. doi: 10.1007/s40121-021-00568-7. Epub 2021 Dec 14.
citation: Rappo U, Gonzalez PL, Puttagunta S, Akinapelli K, Keyloun K, Gillard P, Liu Y, Dunne MW. Single-dose dalbavancin and patient satisfaction in an outpatient setting in the treatment of acute bacterial skin and skin structure infections. J Glob Antimicrob Resist. 2019 Jun;17:60-65. doi: 10.1016/j.jgar.2019.02.007. Epub 2019 Feb 20.
citation: Dunne MW, Puttagunta S, Giordano P, Krievins D, Zelasky M, Baldassarre J. A Randomized Clinical Trial of Single-Dose Versus Weekly Dalbavancin for Treatment of Acute Bacterial Skin and Skin Structure Infection. Clin Infect Dis. 2016 Mar 1;62(5):545-51. doi: 10.1093/cid/civ982. Epub 2015 Nov 26.