AzTrials
AzTrials

Urinary Tract Infection ComplicatedPhase 3NCT02168946

Efficacy, Safety, Tolerability of Vabomere Compared to Best Available Therapy in Treating Serious Infections in Adults

A Phase 3 study testing Vabomere and Best Available Therapy in people with Urinary Tract Infection Complicated and Acute Pyelonephritis, run by Rempex (a wholly owned subsidiary of Melinta Therapeutics, Inc.) at 50 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Vabomere™, (meropenem-vaborbactam) is being compared to the Best Available Therapy in the treatment of adults with selected serious infections due to Carbapenem Resistant Enterobacteriaceae Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Vabomere and Best Available Therapy
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
77 participants
Where
50 sitesin 8 countries
Study dates
Jul 2014to 21 Jul 2017
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Willingness to comply with all study activities and procedures and to provide signed, written informed consent prior to any study procedures. If a subject is unable to provide informed consent due to their medical condition, the subject's legal representative will be provided with study information in order for consent to be obtained.
  • Hospitalized male or female, ≥18 years of age.
  • Weight ≤185 kg.
  • Have a confirmed diagnosis of a serious infection, specifically cUTI or AP, cIAI, HABP, VABP, and/or bacteremia, requiring administration of IV antibacterial therapy.
  • Have a known or suspected Carbapenem-Resistant Enterobacteriaceae (CRE) infection.
  • Expectation, in the opinion of the Investigator, that the subject's infection will require treatment with IV antibiotics for a minimum of 7 days.
Show all 11Show fewer
  • Expectation that subjects with an estimated creatinine clearance <10 ml/min (Cockcroft-Gault) will receive hemodialysis at least 2 times per week.
  • For cUTI \& AP subjects only: expectation, in the judgment of the Investigator, that any indwelling urinary catheter or instrumentation (including nephrostomy tubes and/or indwelling stents) will be removed or replaced (if removal is not clinically acceptable) before or as soon as possible, but not longer than 12 hours, after randomization.
  • For cIAI subjects only: • Expectation, in the judgment of the investigator, that operative drainage/debridement/removal (including open laparotomy, percutaneous drainage, or laparoscopic surgery) of any intra-abdominal collection or other potential source of intra abdominal infection will be performed;
  • Expectation that cultures from the aforementioned procedure (including open laparotomy, percutaneous drainage, or laparoscopic surgery) will be sent for microbiological evaluation, including gram stain, culture and susceptibility testing, and Vabomere susceptibility testing.
  • Female subjects of childbearing potential, including those who are less than 2 years post menopausal, must agree to, and comply with, using 2 highly effective methods of birth control (i.e., condom plus spermicide, combined oral contraceptive, implant, injectable, indwelling intrauterine device, sexual abstinence, or a vasectomized partner) while participating in this study. In addition, all women of childbearing potential must agree to continue to use 2 forms of birth control throughout the study and for at least 30 days after administration of the last dose of study drug.

Who cannot join

  • History of any significant hypersensitivity or severe allergic reaction to any beta-lactam antibiotics (e.g., cephalosporins, penicillins, carbapenems, or monobactams).
  • Known or suspected likely infection with New Delhi metallo- (NDM), Verona integron-encoded metallo- (VIM), or IMP-metallo-beta-lactamases or oxacillinase- (OXA)-beta-lactamases (i.e., Class B or Class D beta-lactamases).
  • For subjects to be enrolled with the primary indication of cUTI or AP, any of the following urologic conditions:
  • Likely to receive ongoing antibacterial drug prophylaxis after treatment of cUTI (e.g., subjects with vesico-ureteral reflux);
  • Suspected or confirmed prostatitis;
  • Requirement for bladder irrigation with antibiotics or for antibiotics to be administered directly via urinary catheter;
Show all 37Show fewer
  • Previous or planned cystectomy or ileal loop surgery;
  • Uncomplicated urinary tract infection (for example, female subjects with urinary frequency, urgency or pain or discomfort without systemic symptoms or signs of infection);
  • Complete, permanent obstruction of the urinary tract;
  • Suspected or confirmed perinephric or renal corticomedullary abscess;
  • Polycystic kidney disease; or
  • Any recent history of trauma to the pelvis or urinary tract.
  • For subjects to be enrolled with the primary indication of cIAI, any of the following conditions:
  • Incomplete drainage of suspected or known intra-abdominal source;
  • Likely to receive ongoing antibacterial drug prophylaxis or chronic suppressive therapy after intravenous treatment of cIAI;
  • Source of infection thought to be related to or involving a non-removable prosthesis (e.g. intra-abdominal mesh) or implantable device, line (e.g. peritoneal catheter) or stent (e.g. biliary stent);
  • Uncomplicated intra-abdominal infection, such as simple appendicitis, simple cholecystitis or gangrenous cholecystitis without rupture;
  • Patients with infected necrotizing pancreatitis or pancreatic abscess;
  • Patients whose surgery will include staged abdominal repair or "open abdomen" technique, or marsupialization (i.e. patients who undergo a surgical procedure where fascial closure is performed are eligible. The skin incision may be left open for purposes of wound management as long as fascial closure is accomplished);
  • Patients in whom the intra-abdominal process is deemed not likely to be infectious in origin (e.g. bowel obstruction, ischemic bowel without perforation, traumatic bowel perforation within past 12 hours, perforated gastroduodenal ulcer within 24 hours); or
  • Non-intra-abdominal infection (e.g. infection or abscess of the abdominal wall without extension into the intra-abdominal cavity).
  • For subjects to be enrolled with the primary indication of HABP or VABP, any of the following conditions:
  • Diagnosis of ventilator-associated tracheobronchitis
  • Inability to obtain proper respiratory specimens for culture.
  • For subjects to be enrolled with the indication of bacteremia unrelated to cUTI or AP, cIAI, HABP, and VABP, any of the following:
  • Unverified CRE infection
  • Source of infection thought to be related to or involving a non-removable or implantable device or line.
  • Evidence of immediately life-threatening disease where in the opinion of the Investigator, the subject is unlikely to survive more than 72 hours from randomization.
  • Acute Physiology and Chronic Health Evaluation (APACHE) II score >30.
  • Known or suspected endocarditis, meningitis, intra-abdominal infection, or osteomyelitis.
  • Irremovable or implantable device or line thought to be the potential source of infection.
  • Evidence of significant hepatic, hematological, or immunologic disease or dysfunction.
  • Women who are pregnant or breastfeeding.
  • Require the use of inhaled antibiotics.
  • Participation in any study involving administration of an investigational agent or device within 30 days prior to randomization into this study or previous participation in the current study.
  • Previous participation in a study of vaborbactam.
  • Any condition that, in the opinion of the Investigator, would compromise the safety of the subject or the quality of the data.

Trial locations and contacts

50 sites in 8 countries.

50 sites in 8 countries

United States20 sites

  • Study site

    Augusta, Georgia, 30912

  • Study site

    Buffalo, New York, 14215

  • Study site

    Charlotte, North Carolina, 28207

  • Study site

    Charlottesville, Virginia, 22908

  • Study site

    Chicago, Illinois, 60611

  • Study site

    Chicago, Illinois, 60612

  • Study site

    Cleveland, Ohio, 44106

  • Study site

    Detroit, Michigan, 48201

  • Study site

    Durham, North Carolina, 27710

  • Study site

    Evanston, Illinois, 60201

  • Study site

    Flushing, New York, 11355

  • Study site

    Hartford, Connecticut, 06102

  • Study site

    Indianapolis, Indiana, 46202

  • Study site

    New Brunswick, New Jersey, 08901

  • Study site

    New York, New York, 10032

  • Study site

    Philadelphia, Pennsylvania, 19104

  • Study site

    Pittsburgh, Pennsylvania, 15213

  • Study site

    Royal Oak, Michigan, 48073

  • Study site

    Tampa, Florida, 33606

  • Study site

    The Bronx, New York, 10467

Other trials in United States

Brazil7 sites

  • Study site

    Belo Horizonte, 30150-221

  • Study site

    Curitiba, 81050-000

  • Study site

    Porto Alegre, 90035-903

  • Study site

    São José do Rio Preto, São Paulo, 05652-900

  • Study site

    São Paulo, 05652-900

  • Study site

    São Paulo, 14048-900

  • Study site

    São Paulo, SP

Other trials in Brazil

Italy6 sites

  • Study site

    Bologna, 40138

  • Study site

    Florence, 50134

  • Study site

    Genova, 16132

  • Study site

    Pisa, 56124

  • Study site

    Rome, 00161

  • Study site

    Udine, 33100

Other trials in Italy

Argentina4 sites

  • Study site

    Buenos Aires, C1405CNF

  • Study site

    Córdoba, 5016

  • Study site

    La Plata, B1900AXI

  • Study site

    Mendoza, 5500

Other trials in Argentina

Greece4 sites

  • Study site

    Athens, 106 76

  • Study site

    Athens, 11527

  • Study site

    Athens, 12462

  • Study site

    Thessaloniki, 54636

Other trials in Greece

Israel4 sites

  • Study site

    Haifa, 31096

  • Study site

    Petah Tikva, 49100

  • Study site

    Ramat Gan, 52621

  • Study site

    Tel Aviv, 64239

Other trials in Israel

Colombia3 sites

  • Study site

    Barranquilla

  • Study site

    Bogotá, 0

  • Study site

    Medellín, 4

Other trials in Colombia

United Kingdom2 sites

  • Study site

    Manchester, M23 9LT

  • Study site

    Manchester, MI39WL

Other trials in United Kingdom

About this study

Official title: A Phase 3, Multi-Center, Randomized, Open-Label Study of Vabomere(Meropenem-vaborbactam) Versus Best Available Therapy in Subjects With Selected Serious Infections Due to Carbapenem-Resistant Enterobacteriaceae (CRE)

Vabomere™, (meropenem-vaborbactam) is being compared to the Best Available Therapy in the treatment of adults with selected serious infections due to Carbapenem Resistant Enterobacteriaceae

Read the detailed description

In the current era of increased resistance to extended spectrum cephalosporins and penicillin/beta-lactamase inhibitor combinations, carbapenem antimicrobial agents are frequently the antibiotics of "last defense" for the most resistant pathogens in serious infections. However, the recent dissemination of serine carbapenemases (e.g. KPC) in Enterobacteriaceae within many hospitals worldwide now poses a considerable threat to carbapenems and other members of the beta-lactam class of antimicrobial agents.

Infections caused by Carbapenem-Resistant Enterobacteriaceae (CRE) are associated with high mortality rates and have limited treatment options. The loss of the carbapenem class of antimicrobial agents for treatment of Enterobacteriaceae (the most frequently occurring pathogens in the hospital setting), Acinetobacter baumannii, and Pseudomonas aeruginosa represents a critical setback in modern patient care.

As a result of the current lack of an optimal treatment for patients who have infections due to a CRE, physicians manage these patients with the limited anti-infective options available, including aminoglycosides, polymyxin B, colistin, tigecycline, or various combinations of these. There are limited efficacy data available for many of these therapies when used to treat serious CRE infections, particularly in combination, but with limited or no alternative therapies currently available, such treatments have become the Best Available Therapy despite the toxicities associated with many of them.

Vaborbactam is a novel beta-lactamase inhibitor that has inhibitory activity against many serine beta-lactamases and was optimized for inhibition of the KPC beta-lactamase and the potentiation of carbapenems against Enterobacteriaceae. Vaborbactam is being developed for use with meropenem (a broad spectrum injectable carbapenem antibiotic) to address the challenges of treatment of serious infections caused by pathogens increasingly resistant to available treatments.

Vabomere, (meropenem-vaborbactam) administered as a fixed combination by intravenous (IV) infusion, is being developed to treat serious gram-negative infections, such as complicated urinary tract infections (cUTI), acute pyelonephritis (AP), hospital-acquired bacterial pneumonia (HABP), ventilator-associated bacterial pneumonia (VABP), and bacteremia, including those infections caused by bacteria resistant to currently available carbapenems.

Being tested
Vabomere, Best Available Therapy
Medical subject headings
Bacteremia, Intraabdominal Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VabomereDrug

    Also called Combination meropenem and vaborbactam, beta-lactamase inhibitor and carbapenem antibiotic

    Vabomere for IV injection, administered as a 2 g/2 g dose

  • Best Available TherapyDrug

    Also called IV Antibiotics

    Antibiotic(s) chosen by Investigator

Study groups in NCT02168946
Study groupRoleWhat they receive
VabomereExperimentalVabomere (meropenem 2g plus vaborbactam 2g) IV q8h, for up to 14 days
Receives: Drug: Vabomere
Best Available TherapyActive comparatorSubjects will receive Best Available Therapy (IV antibiotics)
Receives: Drug: Best Available Therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Proportion of Subjects in the Microbiological Carbapenem-resistant Enterobacteriaceae Modified Intent-to-Treat (mCRE-MITT) Population With a Response of Overall Success [Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP) Subjects]

    Overall success is defined as clinical cure \& microbiological eradication. Eradication defined by FDA as the demonstration that the bacterial pathogen(s) found at baseline is reduced to <10x4 colony forming unit (CFU)/mL urine. Clinical cure defined as complete resolution or significant improvement of the baseline signs \& symptoms, no further antimicrobial warranted.

    Measured: at Test of Cure (TOC) visit (Day 12-23)

  2. All-cause Mortality Rate in the mCRE-MITT Population [Hospital-acquired Bacterial Pneumonia (HABP), Ventilator-associated Bacterial Pneumonia (VABP) and Bacteremia Subjects)

    The All-cause mortality rate at Day 28 in the mCRE-MITT population (HABP/VABP and Bacteremia)

    Measured: Day 28

  3. Proportion of Subjects in the mCRE-MITT Population With a Clinical Outcome of Cure [Complicated Intra-abdominal Infection (cIAI) Subjects Only]

    Clinical cure defined as complete resolution or significant improvement of the baseline signs and symptoms, no further antimicrobial warranted.

    Measured: at TOC visit (Day 12-23)

Secondary outcomes (13)

  1. The All-cause Mortality Rate in the mCRE-MITT Population (All Indications)

    All Cause Mortality at Day 28 in the mCRE-MITT population (all indications)

    Measured: at Day 28

  2. The All-cause Mortality Rate in the m-MITT Population (All Indications)

    The All Cause Mortality rate at Day 28 in the m-MITT population (all indications)

    Measured: at Day 28

  3. The All-cause Mortality Rate in the mCRE-MITT Population (cUTI/AP)

    All Cause Mortality at Day 28 in the mCRE-MITT population (cUTI/AP subjects only)

    Measured: at Day 28

  4. Proportion of Subjects in the mCRE-MITT Population With a Clinical Outcome of Cure (All Indications)

    Clinical cure defined as complete resolution or significant improvement of the baseline signs \& symptoms, no further antimicrobial warranted.

    Measured: at End of Therapy (EOT) visit (7-14 days) and TOC visit (12-23 days)

  5. Proportion of Subjects in the mCRE-MITT Population With a Clinical Outcome of Cure (cUTI/AP Subjects Only)

    Clinical cure defined as complete resolution or significant improvement of the baseline signs \& symptoms, no further antimicrobial warranted.

    Measured: at EOT visit (7-14) and TOC visit (day 12-23)

  6. Proportion of Subjects in the mCRE-MITT Population With a Clinical Outcome of Cure (HABP/VABP and Bacteremia)

    Clinical cure defined as complete resolution or significant improvement of the baseline signs \& symptoms, no further antimicrobial warranted.

    Measured: at EOT visit (7-14) and TOC visit (day 12-23)

  7. Proportion of Subjects in the Microbiological Modified Intent-to-Treat (m-MITT) Population With a Clinical Outcome of Cure (All Indications)

    Clinical cure defined as complete resolution or significant improvement of the baseline signs and symptoms, no further antimicrobial warranted.

    Measured: at EOT visit (7-14) and TOC visit (day 12-23)

  8. Proportion of Subjects in the m-MITT Population With a Clinical Outcome of Cure (cUTI/AP)

    Clinical cure defined as complete resolution or significant improvement of the baseline signs \& symptoms, no further antimicrobial warranted.

    Measured: at EOT visit (7-14) and TOC visit (day 12-23)

  9. Proportion of Subjects in the m-MITT Population With a Clinical Outcome of Cure (HABP/VABP and Bacteremia)

    Clinical cure defined as complete resolution or significant improvement of the baseline signs \& symptoms, no further antimicrobial warranted.

    Measured: at EOT visit (7-14) and TOC visit (day 12-23)

  10. Proportion of Subjects in the mCRE-MITT Population With a Microbiological Outcome of Eradication (All Indications)

    Includes subjects with microbiologic eradication or presumed eradication as defined: microbiologic eradication of the baseline pathogen or absence of culture result (microbiologic outcome of indeterminate or not assesses) where subject is deemed as clinical cure at that visit. For cUTI/AP subjects, demonstration that the bacterial pathogen(s) found at baseline is reduced to <10x4 CFU/mL urine (FDA).

    Measured: at EOT visit (7-14) and TOC visit (day 12-23)

  11. Proportion of Subjects in the m-MITT Population With a Microbiological Outcome of Eradication (All Indications)

    Microbiological eradication defined for cUTI/AP as the demonstration that the bacterial pathogen(s) found at baseline is reduced to <10x4 CFU/mL urine (FDA).

    Measured: at EOT visit (7-14) and TOC visit (day 12-23)

  12. Proportion of Subjects in the m-MITT Populations With a With a Response of Overall Success (cUTI/AP)

    Proportion of subjects in m-MITT Population with response of cure and microbiological eradication or presumed eradication. Eradication defined for cUTI/AP as the demonstration that the bacterial pathogen(s) found at baseline is reduced to <10x4 CFU/mL urine (FDA). Clinical cure defined as complete resolution or significant improvement of the baseline signs \& symptoms, no further antimicrobial warranted.

    Measured: at EOT visit (7-14) and TOC visit (day 12-23)

  13. Proportion of Subjects in the m-MITT Populations With a With a Response of Overall Success (Bacteremia Only)

    Proportion of subjects in m-MITT Population with response of cure and microbiological eradication or presumed eradication. Clinical cure defined as complete resolution or significant improvement of the baseline signs \& symptoms, no further antimicrobial warranted.

    Measured: at EOT visit (7-14) and TOC visit (day 12-23)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Jun 2014 (estimated)
  2. Study startJul 2014
  3. Primary completion21 Jul 2017
  4. Study completion21 Jul 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
77 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02168946
Sponsor's protocol ID
Rempex 506
Status last verified
Feb 2019
First submitted
18 Jun 2014
Last updated
4 Mar 2019
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Bhowmick T. Clinical Outcomes of Patient Subgroups in the TANGO II Study. Infect Dis Ther. 2021 Mar;10(1):35-46. doi: 10.1007/s40121-021-00405-x. Epub 2021 Feb 9.

    PubMed 33565042

  • Wunderink RG, Giamarellos-Bourboulis EJ, Rahav G, Mathers AJ, Bassetti M, Vazquez J, Cornely OA, Solomkin J, Bhowmick T, Bishara J, Daikos GL, Felton T, Furst MJL, Kwak EJ, Menichetti F, Oren I, Alexander EL, Griffith D, Lomovskaya O, Loutit J, Zhang S, Dudley MN, Kaye KS. Effect and Safety of Meropenem-Vaborbactam versus Best-Available Therapy in Patients with Carbapenem-Resistant Enterobacteriaceae Infections: The TANGO II Randomized Clinical Trial. Infect Dis Ther. 2018 Dec;7(4):439-455. doi: 10.1007/s40121-018-0214-1. Epub 2018 Oct 1.

    PubMed 30270406

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Vabomere and Best Available Therapy in people with Urinary Tract Infection Complicated and Acute Pyelonephritis, run by Rempex (a wholly owned subsidiary of Melinta Therapeutics, Inc.) at 50 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 50 sites in United States, Brazil, Italy, Argentina, Greece and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Dec 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of Subjects in the Microbiological Carbapenem-resistant Enterobacteriaceae Modified Intent-to-Treat (mCRE-MITT) Population With a Response of Overall Success [Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP) Subjects] (time frame: at Test of Cure (TOC) visit (Day 12-23)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02168946, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2019.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in