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

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

Overview

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.

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.

Interventions

• 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.
• 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

Primary outcome measures

• 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]
• 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]

Secondary outcome measures (7)

• Incidence of Acute Bacterial Sinusitis [Time frame: 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) [Time frame: 1-2 and 3-4 weeks post-surgery]
• 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]
• 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]
• 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]
• 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]
• Sinusitis and antibiotic resistance as evidenced headache [Time frame: 1 week, 2 weeks, 3 weeks, 4 weeks, 8 weeks, and 12 weeks post-surgery]

Eligibility 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

United States · 1 center

• Barrow Brain and Spine — Phoenix

Identifiers

NCT: NCT03014687 · PHX-16-0134-30-12

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗