Clinical trial NCT03218800: Ertapenem Administered Subcutaneously Versus Intravenously
Official title: Ertapenem Administered Subcutaneously Versus Intravenously for Urinary Tract Infections in Oncological Palliative Care Patients: a Randomized, Open, Non-inferiority Clinical Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Urinary Tract Infections
Keywords: subcutaneous
ertapenem
urinary tract infection
advanced cancer
palliative care
Lead sponsor: Instituto Nacional de Cancer, Brazil
Sponsor class: OTHER_GOV
First posted: 2017-07-17
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Infections requiring intravenous antimicrobial therapy are very common events in patients with advanced cancer. Nevertheless, these patients frequently present vascular damages becoming extremely difficult to access and maintain intravenous route for hydration and nutritional support. In this context, the subcutaneous route could be implemented as an alternative route for replacement of fluids, electrolytes and drugs. Few studies have evaluated the possibility of using the subcutaneous route for treatment of infections though.

Patients in palliative care often have infections caused by multidrug resistant bacterial such as beta-lactamase producing bacteria. In this context, we hypothesize Ertapenem subcutaneously is not inferior to the same drug intravenously for the treatment of urinary infections in patients on oncologic palliative care. A non-inferiority clinical trial would be adequate and could provide stronger evidence on the possibility of this alternative route for antibiotic therapy in urinary tract infections, with important advantages such as greater convenience of use.

Detailed description: This is a randomized open label clinical trial to evaluate Ertapenem administered subcutaneously is non-inferior to the same antibiotic intravenously to treat urinary tract infections in oncological palliative care patients.

The study will be performed at the Palliative Care Unit (PCU) of the National Cancer Institute of Brazil José Alencar Gomes da Silva (INCA), a 56-bed hospital and the only public hospital for cancer palliative care located in the city of Rio de Janeiro, Brazil.

A sample of 82 patients was estimated, considering the level of significance (alpha) of unilateral 2.5%, the power of the study (1-beta) of 80%, the non-inferiority limit of 4%, and success percentages in the groups control and experimental studies of 92% and 100%, respectively. Once the high mortality rate of the study site (about 60%, according to unpublished administrative information), it was decided to increase this number by 30% to compensate for possible losses, totaling 106 patients, 53 in each arm.

Eligibility criteria: Inclusion Criteria:

* Any type of cancer in palliative care;
* Urinary tract infection;
* Informed consent assigned by the patient or legal representative.

Exclusion Criteria:

* Neutropenia;
* Unconsciousness.

Primary outcomes:
measure: microbiological cure
timeFrame: seven days for cystitis and fourteen days for pyelonephritis
Secondary outcomes:
measure: adverse events
timeFrame: 30 days
measure: clinical response
timeFrame: 14 days
Other outcomes:
Locations:
city: Rio de Janeiro
country: Brazil
facility: INCA Instituto Nacional do Cancer
Study officials:
affiliation: INCA- Instituto Nacional de Câncer
name: Luciana Ramadas
role: STUDY_CHAIR
References:
citation: Forestier E, Gros S, Peynaud D, Levast M, Boisseau D, Ferry-Blanco C, Labe A, Lecomte C, Rogeaux O. [Ertapenem administered intravenously or subcutaneously for urinary tract infections caused by ESBL producing enterobacteriacea]. Med Mal Infect. 2012 Sep;42(9):440-3. doi: 10.1016/j.medmal.2012.07.005. Epub 2012 Aug 25. French.
citation: Frasca D, Marchand S, Petitpas F, Dahyot-Fizelier C, Couet W, Mimoz O. Pharmacokinetics of ertapenem following intravenous and subcutaneous infusions in patients. Antimicrob Agents Chemother. 2010 Feb;54(2):924-6. doi: 10.1128/AAC.00836-09. Epub 2009 Nov 23.
citation: Grigoryan L, Trautner BW, Gupta K. Diagnosis and management of urinary tract infections in the outpatient setting: a review. JAMA. 2014 Oct 22-29;312(16):1677-84. doi: 10.1001/jama.2014.12842.
citation: Piaggio G, Elbourne DR, Pocock SJ, Evans SJ, Altman DG; CONSORT Group. Reporting of noninferiority and equivalence randomized trials: extension of the CONSORT 2010 statement. JAMA. 2012 Dec 26;308(24):2594-604. doi: 10.1001/jama.2012.87802.
citation: Tomera KM, Burdmann EA, Reyna OG, Jiang Q, Wimmer WM, Woods GL, Gesser RM; Protocol 014 Study Group. Ertapenem versus ceftriaxone followed by appropriate oral therapy for treatment of complicated urinary tract infections in adults: results of a prospective, randomized, double-blind multicenter study. Antimicrob Agents Chemother. 2002 Sep;46(9):2895-900. doi: 10.1128/AAC.46.9.2895-2900.2002.