Prophylactic Oral Antibiotics on Sinonasal Outcomes Following Endoscopic Transsphenoidal Surgery for Pituitary Lesions (POET)

• ClinicalTrials.gov Identifier: NCT03014687
• Recruitment Status: Recruiting
• First Posted: January 9, 2017
• Last Update Posted: August 15, 2018
• Sponsor: St. Joseph's Hospital and Medical Center, Phoenix
• Collaborators: Thomas Jefferson University; The Cleveland Clinic
• Information provided by (Responsible Party): Pam Dewey, St. Joseph's Hospital and Medical Center, Phoenix

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Antibiotics; Pituitary Adenoma	Drug: Placebo; Drug: Oral Antibiotics cefdinir or trimethoprim/sulfamethoxazole	Phase 4

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 116 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: July 1, 2017
• Estimated Primary Completion Date: January 2019
• Estimated Study Completion Date: July 2019

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: 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.	Drug: Placebo; PO BID placebo for 7 days. Postoperative days 1 through 7: patients will administer saline spray (e.g., Ocean nasal spray) to both nostrils four times daily. Postoperative days 8 through 30: patients will begin twice daily sinus irrigation rinse (e.g., Neti-pot) until day 30. After day 30, patients will perform sinus irrigation as needed. If a patient is unable to tolerate nasal rinses, saline spray can be used as an alternative.; Other Name: inert substance
Experimental: 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.	Drug: Oral Antibiotics cefdinir or trimethoprim/sulfamethoxazole; Oral antibiotics (cefdinir [Omnicef®] 300 mg PO BID or trimethoprim/sulfamethoxazole [Bactrim DS™] PO BID for cephalosporin intolerant patients) for 7 days.Postoperative days 1 through 7: patients will administer saline spray (e.g., Ocean nasal spray) to both nostrils four times daily. Postoperative days 8 through 30: patients will begin twice daily sinus irrigation rinse (e.g., Neti-pot) until day 30. After day 30, patients will perform sinus irrigation as needed. If a patient is unable to tolerate nasal rinses, saline spray can be used as an alternative.; Other Names: Omnicef; Bactrim DS™ cephalosporin intolerant patients

Outcome Measures

Primary Outcome Measures :

1. Change in quality of life from baseline - Anterior Skull Base Nasal Inventory 12 (ASK Nasal-12) [ Time Frame: 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.
2. Change in quality of life from baseline - Sino-Nasal Outcome Test (SNOT-22) [ Time Frame: 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.

Secondary Outcome Measures :

1. Incidence of Acute Bacterial Sinusitis [ Time Frame: 1 week, 2 weeks, 3 weeks, 4 weeks, 8 weeks, and 12 weeks post-surgery ]
   Incidence includes 3 or more of: i. Nasal congestion by patient report or physical exam, ii. Purulent nasal discharge by patient report or physical exam, iii. Facial pressure or pain or headache by patient report, iv. Antibiotics prescribed by a provider for the purpose of treating sinusitis.
2. Changes in endoscopic appearances using Postoperative Debridement Scoring Sheet (modified Lund-Kennedy score) [ Time Frame: 1-2 and 3-4 weeks post-surgery ]
   Postoperative nasal endoscopy findings graded by surgeon. Grading includes Polyps = none 0; middle meatus 1; beyond middle meatus 2. Discharge = none 0; clear and thin 1; thick and purulent 2. Edema = none 0; mild 1; moderate 2; severe 3. Scarring = none 0; mild 1; moderate 2; severe 3. Crusting = none 0; mild 1; moderate 2; severe 3.
3. Sinusitis and antibiotic resistance as evidenced by nasal congestion [ Time Frame: 1 week, 2 weeks, 3 weeks, 4 weeks, 8 weeks, and 12 weeks post-surgery ]
   Cultures and sensitivities when nasal congestion noted by patient report or physical exam.
4. Sinusitis and antibiotic resistance as evidenced by purulent discharge [ Time Frame: 1 week, 2 weeks, 3 weeks, 4 weeks, 8 weeks, and 12 weeks post-surgery ]
   Cultures and sensitivities when purulent nasal discharge noted by patient report or physical exam.
5. Sinusitis and antibiotic resistance as evidenced by pressure [ Time Frame: 1 week, 2 weeks, 3 weeks, 4 weeks, 8 weeks, and 12 weeks post-surgery ]
   Cultures and sensitivities when facial pressure noted by patient report.
6. Sinusitis and antibiotic resistance as evidenced by pain [ Time Frame: 1 week, 2 weeks, 3 weeks, 4 weeks, 8 weeks, and 12 weeks post-surgery ]
   Cultures and sensitivities when facial pain noted by patient report.
7. Sinusitis and antibiotic resistance as evidenced headache [ Time Frame: 1 week, 2 weeks, 3 weeks, 4 weeks, 8 weeks, and 12 weeks post-surgery ]
   Cultures and sensitivities when headache noted by patient report.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 84 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Contacts and Locations

Contacts

Contact: Heidi Jahnke, RN, MSN; 602-406-6976; heidi.jahnke@dignityhealth.org

Locations

United States, Arizona

Barrow Brain and Spine; Recruiting

Phoenix, Arizona, United States, 85013

Contact: Heidi Jahnke, RN,MSN 602-406-6976 heidi.jahnke@dignityhealth.org

Principal Investigator: Andrew Little, MD

Principal Investigator: James Evans, MD

Principal Investigator: Varun Kshettry, MD

Sponsors and Collaborators

St. Joseph's Hospital and Medical Center, Phoenix

Thomas Jefferson University

The Cleveland Clinic

Investigators

• Study Chair: Andrew Little, MD; Barrow Brain and Spine
• Study Chair: James Evans, MD; Thomas Jefferson University

More Information

• Responsible Party: Pam Dewey, Research Manager, St. Joseph's Hospital and Medical Center, Phoenix
• ClinicalTrials.gov Identifier: NCT03014687 History of Changes
• Other Study ID Numbers: PHX-16-0134-30-12
• First Posted: January 9, 2017
• Last Update Posted: August 15, 2018
• Last Verified: August 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Pam Dewey, St. Joseph's Hospital and Medical Center, Phoenix:

transsphenoidal surgery

Additional relevant MeSH terms:

Adenoma; Pituitary Neoplasms; Pituitary Diseases; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Endocrine Gland Neoplasms; Neoplasms by Site; Hypothalamic Neoplasms; Supratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Anti-Bacterial Agents; Cephalosporins; Cefdinir; Trimethoprim, Sulfamethoxazole Drug Combination; Antibiotics, Antitubercular; Trimethoprim; Sulfamethoxazole; Anti-Infective Agents; Antitubercular Agents; Anti-Infective Agents, Urinary; Renal Agents; Antimalarials