Verified January 2017 by St. Joseph’s Hospital and Medical Center, Phoenix
Sponsor:
Collaborators:
Thomas Jefferson University
The Cleveland Clinic
Information provided by (Responsible Party):
Madelon Petersen, St. Joseph’s Hospital and Medical Center, Phoenix
ClinicalTrials.gov Identifier:
NCT03014687
First received: January 4, 2017
Last updated: January 5, 2017
Last verified: January 2017
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.
| Antibiotics Pituitary Adenoma |
Drug: Placebo Drug: Oral Antibiotics cefdinir or trimethoprim/sulfamethoxazole |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, 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 |
- 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 ] [ Designated as safety issue: No ]
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.
Sinonasal quality of life as estimated by patient-reported Anterior Skull Base Nasal Inventory 12 (ASK Nasal-12) and Sino-Nasal Outcomes Test 22 (SNOT-22) rhinologic domain scores, and compared to scores obtained at preoperative baseline. ASK Nasal-12 and SNOT-22 scoring can be completed during a clinic visit or by phone interview.
- 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 ] [ Designated as safety issue: No ]
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.
- Incidence of Acute Bacterial Sinusitis [ Time Frame: 1 week, 2 weeks, 3 weeks, 4 weeks, 8 weeks, and 12 weeks post-surgery ] [ Designated as safety issue: No ]
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.
- Changes in endoscopic appearances using Postoperative Debridement Scoring Sheet (modified Lund-Kennedy score) [ Time Frame: 1-2 and 3-4 weeks post-surgery ] [ Designated as safety issue: No ]
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.
- 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 ] [ Designated as safety issue: No ]
Cultures and sensitivities when nasal congestion noted by patient report or physical exam.
- 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 ] [ Designated as safety issue: No ]
Cultures and sensitivities when purulent nasal discharge noted by patient report or physical exam.
- 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 ] [ Designated as safety issue: No ]
Cultures and sensitivities when facial pressure noted by patient report.
- 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 ] [ Designated as safety issue: No ]
Cultures and sensitivities when facial pain noted by patient report.
- Sinusitis and antibiotic resistance as evidenced headache [ Time Frame: 1 week, 2 weeks, 3 weeks, 4 weeks, 8 weeks, and 12 weeks post-surgery ] [ Designated as safety issue: No ]
Cultures and sensitivities when headache noted by patient report.
| Estimated Enrollment: | 116 |
| Study Start Date: | January 2017 |
| Estimated Study Completion Date: | March 2019 |
| Estimated Primary Completion Date: | January 2019 (Final data collection date for primary outcome measure) |
| 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:
|
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.
| Ages Eligible for Study: | 18 Years to 84 Years (Adult, Senior) |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT03014687
| Barrow Brain and Spine | |
| Phoenix, Arizona, United States, 85013 | |
| Contact: Heidi Jahnke, RN,MSN 602-406-6976 heidi.jahnke@nulldignityhealth.org | |
| Principal Investigator: Andrew Little, MD | |
| Principal Investigator: James Evans, MD | |
| Principal Investigator: Varun Kshettry, MD | |
St. Joseph’s Hospital and Medical Center, Phoenix
Thomas Jefferson University
The Cleveland Clinic
| Study Chair: | Andrew Little, MD | Barrow Brain and Spine |
| Study Chair: | James Evans, MD | Thomas Jefferson University |
| Responsible Party: | Madelon Petersen, Research Clinician, St. Joseph’s Hospital and Medical Center, Phoenix |
| ClinicalTrials.gov Identifier: | NCT03014687 History of Changes |
| Other Study ID Numbers: | PHX-16-0134-30-12 |
| Study First Received: | January 4, 2017 |
| Last Updated: | January 5, 2017 |
| Health Authority: | United States: Food and Drug Administration |
| Individual Participant Data | |
| Plan to Share IPD: | Undecided |
Keywords provided by St. Joseph’s Hospital and Medical Center, Phoenix:
| transsphenoidal surgery |
Additional relevant MeSH terms:
| Pituitary Diseases Adenoma Pituitary Neoplasms Hypothalamic Diseases Brain Diseases Central Nervous System Diseases Nervous System Diseases Endocrine System Diseases Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Endocrine Gland Neoplasms Neoplasms by Site Hypothalamic Neoplasms Supratentorial Neoplasms |
Brain Neoplasms Central Nervous System Neoplasms Nervous System Neoplasms Anti-Bacterial Agents Cefdinir Cephalosporins Trimethoprim, Sulfamethoxazole Drug Combination Antibiotics, Antitubercular Trimethoprim Sulfamethoxazole Anti-Infective Agents Antitubercular Agents Anti-Infective Agents, Urinary Renal Agents Antimalarials |
ClinicalTrials.gov processed this record on January 09, 2017