Single Dose vs. Two Dose Regimen of Dalbavancin for the Treatment of Acute Bacterial Skin and Skin Structure Infections

Surgical Site Infection Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02127970
• Other study ID #: DUR001-303
• Status: Completed
• Phase: Phase 3
• Start date: April 18, 2014
• Est. completion date: March 11, 2015

Study information

• Verified date: August 2018
• Source: Durata Therapeutics Inc., an affiliate of Allergan plc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 698
• Est. completion date: March 11, 2015
• Est. primary completion date: March 11, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Abscess
• Cellulitis
• Communicable Diseases
• Infection
• Surgical Site Infection
• Surgical Wound Infection
• Wound Infection

Intervention

Drug:
• Dalbavancin
Dalbavancin IV infusion over 30 minutes.
• Dalbavancin-matching Placebo
Dalbavancin-matching placebo IV infusion over 30 minutes.

Locations

Country	Name	City	State
Bulgaria	800	Sofia
Bulgaria	801	Sofia
Bulgaria	802	Sofia
Croatia	200	Zagreb
Croatia	201	Zagreb
Estonia	252	Tallinn
Estonia	253	Tallinn
Estonia	251	Tartu
Georgia	302	Kutaisi
Georgia	300	Tbilisi
Georgia	301	Tbilisi
Georgia	303	Tbilisi
Hungary	352	Debrecen
Hungary	353	Kaposvar
Hungary	354	Pecs
Hungary	351	Szeged
Latvia	402	Daugavpils
Latvia	401	Liepaja
Latvia	403	Rezekne
Latvia	400	Riga
Latvia	404	Riga
Romania	500	Bucharest
Romania	502	Bucharest
Romania	503	Bucharest
Romania	501	Cluj-Napoca	Cluj County
Russian Federation	557	Irkutsk
Russian Federation	552	Moscow
Russian Federation	554	Moscow
Russian Federation	553	Novosibirsk
Russian Federation	551	St. Petersburg
Russian Federation	556	Tomsk
Russian Federation	555	Vsevolozhsk	Leningrad Region
Serbia	600	Belgrade
Serbia	601	Belgrade
Serbia	603	Nis
Serbia	602	Novi Sad
South Africa	756	Breyten
South Africa	760	Cape Town
South Africa	752	Dundee
South Africa	755	Johannesburg
South Africa	751	Middleburg
South Africa	758	Port Elizabeth
South Africa	753	Pretoria
South Africa	757	Pretoria
South Africa	759	Pretoria
South Africa	754	Worcester
Ukraine	700	Cherkasy
Ukraine	704	Dnipropetrovsk
Ukraine	701	Ivano-Frankivsk
Ukraine	706	Ivano-Frankivsk
Ukraine	705	Kharkiv
Ukraine	703	Lviv
Ukraine	702	Zaporizhzhya
United States	103	Anaheim	California
United States	114	Augusta	Georgia
United States	121	Butte	Montana
United States	122	Columbus	Georgia
United States	109	Detroit	Michigan
United States	119	Eunice	Louisiana
United States	126	Franklin	Tennessee
United States	106	Long Beach	California
United States	117	Long Beach	California
United States	118	Modesto	California
United States	110	Montgomery	Alabama
United States	123	Omaha	Nebraska
United States	107	Orlando	Florida
United States	120	Saint Cloud	Florida
United States	104	San Diego	California
United States	113	San Diego	California
United States	115	San Diego	California
United States	116	San Diego	California
United States	125	Savannah	Georgia
United States	127	Smyrna	Tennessee
United States	101	Springfield	Massachusetts
United States	108	Stockton	California
United States	105	Sylmar	California
United States	111	Toledo	Ohio
United States	112	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Durata Therapeutics Inc., an affiliate of Allergan plc

Countries where clinical trial is conducted

United States,  Bulgaria,  Croatia,  Estonia,  Georgia,  Hungary,  Latvia,  Romania,  Russian Federation,  Serbia,  South Africa,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percentage of Participants by Clinical Status Based on Localized Fluctuance and Heat/Warmth at End of Treatment (EOT)	Clinical Success was defined as localized fluctuance and heat/warmth that if present at Baseline must be improved and no worse than mild. Clinical Failure was defined as the opposite to success. Clinical status was Indeterminate if any of the data needed to determine clinical success or clinical failure were missing.	EOT (Day 14-15)
Other	Percentage of Participants by Investigator Assessment of Clinical Outcome	A successful outcome was based on resolution or improvement of all signs and symptoms of the infection to such an extent that no further antibacterial treatment was given. An unsuccessful outcome was the opposite of successful. An Indeterminate outcome was defined as any of the data needed to determine a successful or unsuccessful outcome were missing.	Day 3-4, Day 8, EOT (Day 14-15) and Final Visit (Day 28 +/- 2 days)
Other	Percentage of Participants Achieving Clinical Outcome of Success Based on Key Target Pathogen at Baseline	A successful outcome was based on resolution or improvement of all signs and symptoms of the infection to such an extent that no further antibacterial treatment was given.	Day 3-4 and EOT (Day 14-15)
Other	Percentage of Participants With Complete Resolution of Local Signs of Infection	Resolution of Local Signs of Infection that include absence of purulence/drainage, erythema, heat/localized warmth, pain/tenderness to palpation, fluctuance, and swelling/induration.	Day 3-4, Day 8, EOT (Day 14-15) and Final Visit (Day 28 +/- 2 days)
Other	Change From Baseline in Participant's Assessment of Pain	Using the Brief Pain Inventory Scale, participants rated their pain "right now" on a scale where: 0=no pain to 10=pain as bad as you can imagine. A negative change from Baseline indicated improvement.	Baseline (Day 0) to Day 3-4, Day 8, EOT (Day 14-15) and Final Visit (Day 28 + /- 2 days)
Other	Percentage of Participants by Resource Utilization Categories	Resource Utilization Categories included: Any additional visits (including urgent care), Any additional procedures, Any additional tests, Any home visits or nursing care and Any ER Visits. The percentage of participants in each category is reported.	Final Visit (Day 28 +/- 2 days)
Other	Percentage of Participants by Skin and Soft Tissue Infection-Convenience (SSTI-C) Questionnaire: Overall Satisfaction Response	The SSTI-C Questionnaire is an 11-item self-reported questionnaire that measures subjective experiences of the participant. One of the items assessed was overall satisfaction with treatment. Participants answered the question: "Overall, how satisfied were you with your antibiotic treatment?" using one of the following responses: Extremely satisfied, Moderately satisfied, Not at all satisfied, Slightly satisfied and Very satisfied. The percentage of participants in each category is reported.	EOT (Day 14-15)
Primary	Percentage of Participants Who Were Clinical Responders 48-72 Hours After the Initiation of Study Drug	Clinical responder was defined as a participant who was alive and had received no rescue therapy for acute bacterial skin and skin structure infection (ABSSSI) prior to the 48-72 hour infection site assessment (if an antibiotic has been given for another reason, the participant will not be considered a non-responder for this reason); and examination of the participant's ABSSSI lesion demonstrates a decrease of = 20% in lesion area (calculated as the longest length multiplied by the longest perpendicular width) relative to the baseline measurement.	Up to 48-72 hours after the initiation of study drug
Secondary	Percentage of Participants by Clinical Status at End of Treatment (EOT) and Final Visit (FV)	Clinical Success is defined as follows: For evaluation at EOT visit, lesion area must be decreased by =80% from baseline and at FV lesion area must be decreased by =90% from baseline; Temperature is =37.6°C; Local signs of tenderness to palpation and swelling/induration are no worse than mild; For evaluation at EOT visit, local signs of fluctuance and localized heat/warmth must be improved from baseline and no worse than mild, and at FV local signs of fluctuance and localized heat/warmth must be absent; for participants with a wound infection the severity of purulent drainage is improved and no worse than mild relative to baseline. Clinical Failure is defined as the opposite to success or if the participant died during the study period up to visit or received study therapy for ABSSSI beyond the protocol treatment period. Clinical status is Indeterminate if any of the data needed to determine clinical success or clinical failure were missing.	End of Treatment (Day 14-15 after the initiation of study drug) and Final Visit (28 ±2 days after the initiation of study drug)