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

NCT ID: NCT03014687

Last Updated: 2018-08-15

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 116 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-07-01
• Study Completion Date: 2019-07-31

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.

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.

Conditions

Antibiotics; Pituitary Adenoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

Oral Antibiotics cefdinir or trimethoprim/sulfamethoxazole

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

inert substance; Omnicef; Bactrim DS™ cephalosporin intolerant patients

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 84 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Thomas Jefferson University

OTHER

Sponsor Role: collaborator

The Cleveland Clinic

OTHER

Sponsor Role: collaborator

St. Joseph's Hospital and Medical Center, Phoenix

OTHER

Sponsor Role: lead

Responsible Party

Pam Dewey

Research Manager

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Andrew Little, MD

Role: STUDY_CHAIR

Barrow Brain and Spine

James Evans, MD

Role: STUDY_CHAIR

Thomas Jefferson University

Locations

Barrow Brain and Spine

Phoenix, Arizona, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Heidi Jahnke, RN, MSN

Role: CONTACT

heidi.jahnke@dignityhealth.org

602-406-6976

Facility Contacts

Heidi Jahnke, RN,MSN

Role: primary

heidi.jahnke@dignityhealth.org

602-406-6976

Other Identifiers

PHX-16-0134-30-12

Identifier Type: -

Identifier Source: org_study_id