A Multicenter, Randomized, Placebo-Controlled, Double-Blind Study Evaluating the Impact of Prophylactic Oral Antibiotics on Sinonasal Outcomes Following Endoscopic Transsphenoidal Surgery for Pituitary Lesions
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 116
- 试验地点
- 1
- 主要终点
- Change in quality of life from baseline - Sino-Nasal Outcome Test (SNOT-22)
研究概览
简要总结
To find out whether oral antibiotics given after transsphenoidal endoscopic surgery for pituitary adenoma improves sinus and nasal symptoms, reduces the incidence of infection (sinusitis), and helps mucosal healing in the nasal passages.
详细描述
Transsphenoidal surgery is the standard of care for most symptomatic pituitary adenomas. Since transsphenoidal surgery exploits the nasal passage to reach the sella turcica and pituitary gland, the technique causes disruption of sinonasal function and temporarily impacts sinonasal quality of life. Disrupted sinonasal function is a primary source of postoperative morbidity following transsphenoidal surgery. Common sinonasal complications include sinusitis, synechiae formation, nasal obstruction and crusting. The development of postoperative sinusitis is specifically associated with decreased sinonasal function after surgery. Because the nasal cavity is a contaminated surgical field, practitioners routinely prescribe a course of oral postoperative antibiotics for 7-14 days (in addition to standard prophylactic perioperative intravenous antibiotics) with the intention of improving nasal functional outcomes. To date, no studies have examined whether the administration of oral antibiotics following transsphenoidal surgery improves sinonasal healing. This question has been studied in a closely-related field, functional endoscopic sinus surgery (FESS). A meta-analysis of clinical trial data obtained in FESS indicated that current literature does not support the use of oral antibiotics to reduce infection, improve symptoms scores, or improve endoscopic findings. Furthermore, there is the potential for antibiotic-related adverse events including the emergence of bacterial resistance, Clostridium difficile infection, and allergic reactions to the medication. Despite the lack of supporting evidence in FESS, prophylactic antibiotic use for improving sinonasal healing is still common in pituitary surgery. The investigators propose to study whether prophylactic oral antibiotics following transsphenoidal surgery improve sinonasal quality of life, reduce sinusitis incidence, and promote mucosal healing following endoscopic transsphenoidal surgery.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 84 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patient undergoing endoscopic surgery for resection of pituitary tumors for nonfunctioning adenoma, acromegaly, or prolactinoma
- •Adults >18 and <85 years of age
- •English speaking and able to understand the ASK Nasal-12 and SNOT-22 scales
- •Free of any physical, mental, or medical condition which, in the opinion of the investigator, makes study participation inadvisable
排除标准
- •Anaphylaxis/intolerance to the study drugs
- •Cirrhosis, hepatitis
- •Any solid organ transplant or bone marrow transplant. And any patient felt to be immunocompromised by the investigators
- •Renal failure on dialysis
- •Any subject who is unwilling or unable to sign informed consent for the study
- •Pregnancy
- •Incarcerated patients
- •Cushing's disease
- •Rathke's Cleft cyst or pituitary cyst
- •History of chronic sinusitis
- •Anticipated use of nasal splints
- •Anticipated use of nasal septal flap
- •Active sinusitis
- •Nasal polyps
- •Previous sinus surgery
- •Concurrent antibiotics for another indication (i.e., urinary tract infection)
- •Immunodeficiency
研究组 & 干预措施
Standard Nasal Care
One dose of preoperative intravenous (iv) antibiotic (e.g., cefazolin 1gm, or cefuroxime 1.5gm, or clindamycin 300mg will be administered within 60 minutes of start of surgery. Repeat intraoperative dosing of antibiotics is permitted if length of surgery exceeds recommended dosing interval. IV antibiotic dosing schedules: Cefazolin 1 gm iv Q6 hr -or- Cefuroxime 1.5gm iv Q8 hr -or- Clindamycin 300 mg iv Q12 hr. Postoperative antibiotics: Study participants will receive one dose only of postoperative intravenous antibiotic (e.g., cefazolin 1gm, or cefuroxime 1.5gm, or clindamycin 300mg [cephalosporin allergic patients]) according to the recommended dosing schedule described above. This dose of antibiotics is in addition to the preoperative dose. Placebo PO BID (twice daily) will commence on the morning of postoperative day 1 and continue for 7 days.
干预措施: Placebo (Drug)
Standard Nasal Care + Oral Antibiotics
One dose of preoperative iv antibiotic (cefazolin 1gm, or cefuroxime 1.5gm, or clindamycin 300mg) will be administered within 60 minutes of start of surgery. Repeat intraoperative dosing of antibiotics is permitted if length of surgery exceeds recommended dosing interval. IV antibiotic dosing schedules: Cefazolin 1 gm iv Q6 hr -or- Cefuroxime 1.5gm iv Q8 hr -or- Clindamycin 300 mg iv Q12 hr. Participants will receive 1 dose only of postoperative iv antibiotic (cefazolin 1gm, or cefuroxime 1.5gm, or clindamycin 300mg [cephalosporin allergic patients]) according to the recommended dosing schedule described above. This dose of antibiotics is in addition to the preoperative dose. Oral antibiotics will commence on the morning of postoperative day 1; this group will receive oral antibiotics (cefdinir [Omnicef®] 300 mg PO BID or trimethoprim/sulfamethoxazole [Bactrim DS™] PO BID for cephalosporin intolerant patients) for 7 days.
干预措施: Oral Antibiotics cefdinir or trimethoprim/sulfamethoxazole (Drug)
结局指标
主要结局
Change in quality of life from baseline - Sino-Nasal Outcome Test (SNOT-22)
时间窗: 1 week, 2 weeks, 3 weeks, 4 weeks, 8 weeks, and 12 weeks post-surgery
Completed by subject in clinic or by phone interview. Assesses need to blow nose; nasal blockage; sneezing; runny nose; cough; post-nasal discharge; thick nasal discharge; ear fullness; dizziness; ear pain; facial pain/pressure; decreased sense of smell/taste; difficulty falling asleep; waking up at night; lack of a good night's sleep; wake up tired; fatigue; reduced productivity; reduced concentration; frustrated/restless/irritable; sad; and, embarrassed. Rating choices include no problem 0; very mild problem 1; mild or slight problem 2; moderate problem 3; severe problem 4; problem as bad as it can be 5. Subject also selects the 5 symptoms/items listed that impact life the most.
Change in quality of life from baseline - Anterior Skull Base Nasal Inventory 12 (ASK Nasal-12)
时间窗: 1 week, 2 weeks, 3 weeks, 4 weeks, 8 weeks, and 12 weeks post-surgery
Completed by subject in clinic or by phone interview. Assesses urge to blow nose; post-nasal discharge; thick nasal discharge; headaches; nose makes whistling sound; nasal crusting; trouble breathing through nose during day; trouble breathing through nose during night; not breathing equally in both nostrils; sense of smell; sense of taste; and, overall functioning of nose.Rating choices include no problem 0; very minor problem 1; minor problem 2; moderate problem 3; moderately severe problem 4; and, severe problem 5. Subject also selects the 5 symptoms/items listed that impact life the most.
次要结局
- Incidence of Acute Bacterial Sinusitis(1 week, 2 weeks, 3 weeks, 4 weeks, 8 weeks, and 12 weeks post-surgery)
- Changes in endoscopic appearances using Postoperative Debridement Scoring Sheet (modified Lund-Kennedy score)(1-2 and 3-4 weeks post-surgery)
- Sinusitis and antibiotic resistance as evidenced by nasal congestion(1 week, 2 weeks, 3 weeks, 4 weeks, 8 weeks, and 12 weeks post-surgery)
- Sinusitis and antibiotic resistance as evidenced by purulent discharge(1 week, 2 weeks, 3 weeks, 4 weeks, 8 weeks, and 12 weeks post-surgery)
- Sinusitis and antibiotic resistance as evidenced by pressure(1 week, 2 weeks, 3 weeks, 4 weeks, 8 weeks, and 12 weeks post-surgery)
- Sinusitis and antibiotic resistance as evidenced by pain(1 week, 2 weeks, 3 weeks, 4 weeks, 8 weeks, and 12 weeks post-surgery)
- Sinusitis and antibiotic resistance as evidenced headache(1 week, 2 weeks, 3 weeks, 4 weeks, 8 weeks, and 12 weeks post-surgery)
研究者
Pam Dewey
Research Manager
St. Joseph's Hospital and Medical Center, Phoenix