[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100658414":3},{"organization":4,"outcomesModule":7,"designInfo":37,"detailedDescription":45,"studyPopulation":36,"armGroups":46,"interventions":59,"overallOfficials":36,"centralContacts":68,"locations":78,"responsibleParty":96,"collaborators":36,"id":100,"slug":101,"hasResults":102,"nctId":103,"briefTitle":104,"officialTitle":105,"acronym":106,"eligibilityCriteria":107,"healthyVolunteers":102,"sex":108,"minAge":109,"maxAge":36,"enrollmentInfo":110,"targetDuration":36,"studyType":113,"phases":114,"briefSummary":116,"conditions":117,"keywords":122,"overallStatus":81,"whyStopped":36,"lastUpdateSubmitDate":130,"lastUpdatePostDateStruct":131,"startDateStruct":134,"completionDateStruct":136,"leadSponsor":138,"locationsCount":139},{"fullName":5,"class":6},"AC Camargo Cancer Center","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":13,"otherOutcomes":36},[9],{"measure":10,"description":11,"timeFrame":12},"Incidence of Surgical Site Infection","Proportion of participants in each arm who develop a surgical site infection (SSI) within 30 days after surgery. SSI is diagnosed when at least one of the following is present: (1) purulent drainage from the incision; (2) a positive culture from fluid or tissue at the incision obtained with aseptic technique; or (3) a diagnosis of SSI by the attending surgeon or physician. The groups are compared using the chi-square test (intention-to-treat analysis).","From surgery through postoperative day 30",[14,18,22,26,30,33],{"measure":15,"description":16,"timeFrame":17},"Secondary Outcome Measure [*]","Number of days the participant stays in the intensive care unit (ICU) during the surgical admission.","From surgery through hospital discharge, up to 30 days after surgery",{"measure":19,"description":20,"timeFrame":21},"Hospital Length of Stay","Number of days from hospital admission for surgery to hospital discharge.","From hospital admission through discharge, up to 30 days after surgery",{"measure":23,"description":24,"timeFrame":25},"Hospital Readmission Rate","Proportion of participants readmitted to the hospital for clinical or surgical complications within 30 days after discharge from the surgical admission. Planned admissions for adjuvant treatment (such as placement of a chemotherapy catheter) are not counted.","Within 30 days after hospital discharge",{"measure":27,"description":28,"timeFrame":29},"Emergency Department Visit Rate","Proportion of participants who make at least one unscheduled emergency department visit after discharge from the surgical admission.","Within 30 days after surgery",{"measure":31,"description":32,"timeFrame":21},"Total Hospitalization Cost","Total cost of the surgical admission, in Brazilian reais (BRL), including direct costs (materials, drugs, professional fees) and indirect costs (allocated by absorption costing). Micro-costing is used, from the payer perspective.",{"measure":34,"description":35,"timeFrame":12},"Incidence of Serious Adverse Events","Proportion of participants with serious treatment-related adverse events, graded using the Common Terminology Criteria for Adverse Events (CTCAE). These include infections other than SSI (for example Clostridioides difficile infection or pneumonia), allergic reactions, acute kidney injury, and other antibiotic-related toxicity.",null,{"allocation":38,"interventionModel":39,"interventionModelDescription":40,"primaryPurpose":41,"observationalModel":36,"timePerspective":36,"maskingInfo":42},"RANDOMIZED","PARALLEL","This is a randomized, open-label, parallel-group superiority trial. Eligible adults scheduled for major head and neck cancer surgery or microvascular free-flap reconstruction are assigned 1:1, using a maximum tolerated imbalance procedure (imbalance limit of 3), to one of two groups: standard 24-hour postoperative antibiotic prophylaxis or extended 7-day postoperative prophylaxis with ampicillin\u002Fsulbactam. Both groups receive the same preoperative decolonization and the same antibiotic dosing before and during surgery; the groups differ only in how long the antibiotic continues after surgery. Participants stay in their assigned group for the whole study and are followed for 30 days after surgery.","PREVENTION",{"masking":43,"maskingDescription":44,"whoMasked":36},"NONE","This is an open-label study. Participants, care providers, investigators, and outcome assessors are not masked, because the two groups get the antibiotic for different lengths of time after surgery (24 hours vs. 7 days), which makes blinding impossible. To reduce bias, the primary outcome (surgical site infection) uses predefined objective criteria: purulent drainage, positive culture, or diagnosis by the attending physician. The statistical analysis follows the intention-to-treat principle.","Background and Rationale\n\nSurgical site infection (SSI) is a common and serious complication of major head and neck cancer surgery. Operations such as mandibulectomy, pharyngolaryngectomy, and major glossectomy, and procedures that need microvascular free-flap or pedicled flap reconstruction, expose the neck to bacteria from the oral cavity and upper aerodigestive tract for many hours. Several other factors add to the risk: tumor-associated oral dysbiosis, long operative times, flap ischemia, dead space, previous radiotherapy, malnutrition, tobacco and alcohol use, and tracheostomy. As a result, reported SSI rates in these operations range from 20% to 50%. That is much higher than expected for clean-contaminated procedures and closer to the rates seen in infected procedures. SSI is linked to fistula, flap failure, reoperation, longer hospital stays, delays in adjuvant treatment, and higher costs.\n\nCenters for Disease Control and Prevention (CDC) and World Health Organization (WHO) guidelines advise against continuing antibiotic prophylaxis after surgery ends. However, these guidelines do not address the specific risk factors of head and neck reconstruction, and these patients are underrepresented in the trials behind them. Practice varies widely: in one survey of microvascular surgeons, 5 days of prophylaxis was the most common duration, and some authors recommend 7 days for free-flap cases. Retrospective studies disagree about whether longer courses help, and no randomized evidence exists. Data from low- and middle-income countries, where SSI rates are higher, are especially limited.\n\nAt the study institution, SSI indicators have been collected prospectively since 2014. SSI rates in major and free-flap head and neck procedures stayed between 33% and 50.9%. This was true even after the prophylactic regimen was changed from clindamicin plus ceftriaxone to ampicillin\u002Fsulbactam in 2022, and after a preoperative decolonization protocol was introduced. In a previous prospective cohort of 401 patients, the overall SSI rate was 41.9%. This trial tests whether extending postoperative prophylaxis lowers SSI and length of stay in this high-risk group.\n\nStudy Design\n\nSingle-center, pragmatic, open-label, randomized, parallel-group superiority trial. The trial is pragmatic because both regimens are already used in clinical practice. Blinding is not feasible because the arms differ in how long the postoperative antibiotic is given.\n\nRandomization\n\nPatients are allocated 1:1 using a maximum tolerated imbalance (MTI) procedure with an imbalance limit of 3. When the limit is reached, the next patient is assigned to the smaller arm. This lowers the predictability of allocation while keeping the arms balanced. Allocation is generated dynamically in REDCap after enrollment, and patients do not cross over between arms.\n\nStandardized Perioperative Care (Both Arms)\n\nPreoperative decolonization for 5 days: 0.12% chlorhexidine oral rinse three times a day, 2% chlorhexidine body wash once a day, and nasal mupirocin three times a day.\n\nPreoperative consultations with nursing, nutrition (with supplementation when needed), and oral medicine.\n\nIn the operating room: 2-minute skin antisepsis of the resection and donor sites with 2% chlorhexidine or 10% povidone-iodine, plus oral and pharyngeal cleansing with 0.12% chlorhexidine.\n\nThe first antibiotic dose is given at anesthesia induction, 10 to 60 minutes before skin incision, and redosed every 4 hours during surgery.\n\nData Collection\n\nData are collected from the electronic medical record with a standardized case report form and entered in REDCap. Variables include:\n\nDemographics and lifestyle: age, sex, smoking (pack-years), alcohol use. Clinical data: comorbidities, American Society of Anesthesiologists Physical Status Classification System, Body Mass Index.\n\nTumor data: site, histology, UICC-TNM stage, prior radiotherapy or chemotherapy.\n\nSurgical data: main procedure, type of reconstruction, flap ischemia time (from pedicle ligation to completion of the anastomoses), operative time (from skin incision to dressing), salvage surgery, and perioperative blood transfusion.\n\nCost Analysis\n\nCosts are taken from the institution's patient-level billing database (Base de Atendimento) for the index surgical admission. Direct costs are materials, drugs, and professional fees. Indirect costs are allocated by absorption costing and include idle capacity. The analysis follows the Brazilian Ministry of Health guidelines for economic evaluation, takes the payer perspective, and uses micro-costing. Unit prices come from public procurement references: BEC\u002FSP and the Ministry of Health Health Price Database.\n\nStatistical Analysis\n\nAnalyses follow the intention-to-treat principle and are done in R and Python. Categorical variables are compared with the chi-square test and continuous variables with Student's t-test. Multivariable analysis uses Cox proportional hazards models, with the proportional hazards assumption checked by Schoenfeld residuals.\n\nSample Size The sample size was calculated for the primary outcome (30-day SSI) as a comparison of two independent proportions. The SSI rate in the control group was assumed to be 43%, based on the institutional prospective cohort of patients undergoing major head and neck surgery. An SSI rate of 12% was expected in the intervention group, which is an absolute reduction of 31 percentage points.\n\nWith a two-sided significance level of 5% and 80% power, at least 32 evaluable patients per group are needed. Allowing for an estimated 10% loss to follow-up, the sample was set at 40 patients per group, for a total of 80 participants. The calculation was done in G\\*Power, version 3.1.9.7.\n\nInterim Safety Analysis\n\nA safety analysis will be done once 50% of the planned patients have completed 30 days of follow-up. Adverse events are graded using CTCAE. The two arms will be compared for serious treatment-related complications, including infections other than SSI (such as Clostridioides difficile), drug toxicity, and allergic reactions. If the difference in serious adverse event rates between the arms is greater than 20%, early termination or protocol changes will be considered together with the institutional Infection Prevention and Control Service.",[47,53],{"label":48,"type":49,"description":50,"interventionNames":51},"Standard Prophylaxis (24 Hours)","ACTIVE_COMPARATOR","Participants receive the institutional standard antibiotic prophylaxis with ampicillin\u002Fsulbactam: 3 g IV at anesthesia induction (10 to 60 minutes before skin incision), 3 g IV every 4 hours during surgery, and 3 g IV every 6 hours for 24 hours after surgery. All participants also complete the institutional preoperative decolonization protocol for 5 days before surgery (chlorhexidine oral rinse, chlorhexidine body wash, and nasal mupirocin).",[52],"Drug: Ampicillin\u002FSulbactam 24-Hour Postoperative Prophylaxis",{"label":54,"type":55,"description":56,"interventionNames":57},"Extended Prophylaxis (7 Days)","EXPERIMENTAL","Participants receive ampicillin\u002Fsulbactam 3 g IV at anesthesia induction (10 to 60 minutes before skin incision) and 3 g IV every 4 hours during surgery, the same as the standard group. After surgery, the antibiotic continues at 3 g IV every 6 hours for 7 days, or until hospital discharge if that is sooner. All participants also complete the institutional preoperative decolonization protocol for 5 days before surgery (chlorhexidine oral rinse, chlorhexidine body wash, and nasal mupirocin).\n\nInterventions: ☑ Ampicillin\u002FSulbactam 7-Day Postoperative Prophylaxis",[58],"Drug: Ampicillin\u002FSulbactam 7-Day Postoperative Prophylaxis",[60,64],{"type":61,"name":62,"description":50,"armGroupLabels":63,"otherNames":36},"DRUG","Ampicillin\u002FSulbactam 24-Hour Postoperative Prophylaxis",[48],{"type":61,"name":65,"description":66,"armGroupLabels":67,"otherNames":36},"Ampicillin\u002FSulbactam 7-Day Postoperative Prophylaxis","Participants receive ampicillin\u002Fsulbactam 3 g IV at anesthesia induction (10 to 60 minutes before skin incision) and 3 g IV every 4 hours during surgery, the same as the standard group. After surgery, the antibiotic continues at 3 g IV every 6 hours for 7 days, or until hospital discharge if that is sooner. All participants also complete the institutional preoperative decolonization protocol for 5 days before surgery (chlorhexidine oral rinse, chlorhexidine body wash, and nasal mupirocin).",[54],[69,74],{"name":70,"role":71,"phone":72,"phoneExt":36,"email":73},"Genival Barbosa de Carvalho, PhD","CONTACT","55991447426","genival.carvalho@accamargo.org.br",{"name":75,"role":71,"phone":76,"phoneExt":36,"email":77},"Renata Otoni Neiva, MD","55955835688","renata.otoni@accamargo.org.br",[79],{"facility":80,"status":81,"city":82,"state":82,"zip":83,"country":84,"countryCode":85,"cosmosGeoPoint":86,"geoPoint":91,"contacts":92},"A.C. Camargo Cancer Center","RECRUITING","São Paulo","0509900","Brazil","BR",{"type":87,"coordinates":88},"Point",[89,90],-46.63611,-23.5475,{"lat":90,"lon":89},[93],{"name":94,"role":71,"phone":95,"phoneExt":36,"email":73},"Genival Barbosa de Carvalho, PhD, PhD","11991444726",{"type":97,"investigatorFullName":98,"investigatorTitle":99,"investigatorAffiliation":5,"oldNameTitle":36,"oldOrganization":36},"PRINCIPAL_INVESTIGATOR","Genival Barbosa de Carvalho","PhD","100658414","phase-3-prophylactic-antibiotic-duration-in-head-and-neck-cancer-surgery-a-pragmatic-open-label-randomized-superiority-trial-protect-hn-trial-100658414",false,"NCT07851857","Prophylactic Antibiotic Duration in Head and Neck Cancer Surgery (PROTECT-HN Trial)","Duração da Profilaxia antibiótica em Cirurgia de Grande Porte de cabeça e pescoço; Ensaio clínico Randomizado PROTECT-HN Trial (Prophylactic Antibiotic Duration in Head and Neck Cancer Surgery Trial)","PROTECT-HN","Inclusion Criteria:\n\n* Age 18 years or older\n* Diagnosis of cancer of the oral cavity or pharynx\n* Scheduled for major head and neck surgery (e.g., mandibulectomy, pharyngolaryngectomy, major glossectomy) and\u002For reconstruction with a microvascular free flap or pedicled flap\n* Communication between the primary tumor site and the neck during surgery (direct exposure of the neck to oral or pharyngeal contents)\n* Signed informed consent\n\nExclusion Criteria:\n\n* Known allergy to ampicillin\u002Fsulbactam, penicillins, or other beta-lactam antibiotics\n* Infected surgical field, or active infection needing therapeutic antibiotics at the time of surgery\n* Refusal to participate","ALL","18 Years",{"count":111,"type":112},80,"ESTIMATED","INTERVENTIONAL",[115],"PHASE3","The goal of this clinical trial is to learn whether giving antibiotics for 7 days after surgery, instead of the usual 24 hours, lowers the chance of wound infection in adults having major surgery for mouth or throat cancer. This includes operations that rebuild the area with tissue taken from another part of the body (free-flap reconstruction).\n\nThe main question it aims to answer is:\n\nDoes a 7-day course of antibiotics after surgery lower the number of patients who get a surgical wound infection within 30 days, compared with the standard 24-hour course?\n\nOther questions are:\n\nDoes the longer course shorten the time spent in the intensive care unit and in the hospital? Does it lower the number of emergency room visits, hospital readmissions, and hospital costs within 30 days? Is the longer course safe, and does it cause more side effects?\n\nResearchers will compare two groups. Both groups receive the same antibiotic (ampicillin\u002Fsulbactam) through a vein before and during surgery. After surgery, one group continues the antibiotic for 24 hours (the current standard), and the other group continues it for 7 days, or until they go home if that is sooner.\n\nParticipants will:\n\nBe assigned by chance (like flipping a coin) to one of the two groups Follow the hospital's usual care before surgery, including mouthwash, antiseptic body wash, and nasal ointment for 5 days Receive the antibiotic according to their group Be followed for 30 days after surgery to check for wound infection, other complications, return visits, and readmissions",[118,119,120,121],"Surgical Wound Infection","Head and Neck Neoplasms","Oral Cancer Neoplasms","Pharyngeal Neoplasms",[123,124,125,126,127,128,129],"Antibiotic Prophylaxis","Extended Antibiotic Prophylaxis","Surgical Site Infection","Head and Neck Surgery","Length of Stay","Hospital Costs","Pragmatic Clinical Trial","2026-10-01",{"date":132,"type":133},"2026-10-05","ACTUAL",{"date":135,"type":133},"2025-05-29",{"date":137,"type":112},"2028-05-30",{"name":5,"class":6},1]