Doxycycline in Treating Patients With Chronic Rhinosinusitis With Nasal Polyps

The Role of Doxycycline in Management of Moderate to Severe Chronic Rhinosinusitis With Nasal Polyps

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02569437

Enrollment

Registered

2015-10-06

Start date

2014-09-30

Completion date

2016-08-31

Last updated

2018-01-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Polyp of Nasal Sinus

Keywords

doxycycline, oral methylprednisone, sinusitis with nasal polyps

Brief summary

The Department of Otolaryngology at Mount Sinai is looking for adults with sinus disease with polyps, otherwise called chronic rhinosinusitis with nasal polyps (CRSwNP). Patients may be eligible to enroll in a study offering a cutting-edge therapy to help reduce symptoms and avoid surgery. The treatment combines an antibiotic (doxycycline) with oral steroids. Oral steroids are the mainstay of medical management for patients with CRSwNP. However, recent studies have shown that doxycycline helps improve symptoms as well by reducing inflammation and killing common bacteria that can cause symptoms. This study is the first to evaluate this combination regimen.

Detailed description

An eligible patient may be treated with either doxycycline and oral steroids OR placebo (sugar pill) and oral steroids for three weeks. Volunteers will participate in the study for to 12 weeks, and will have 4 research visits of 1 hour duration. At each study visit, the patient will under go an endoscopic evaluation and asked to complete a questionnaire describing symptoms. There is no additional cost to be enrolled in the study.

Interventions

DRUGDoxycycline

Doxycycline (200 mg PO X 1 dose on Day 1, then 100 mg PO daily) for Day 2-20

DRUGmethylprednisolone

oral methylprednisolone: 32 mg x 5 days, 16 mg x 5 days, 8 mg x 10 days

DRUGnasal saline spray

nasal saline sprays: 2 sprays each nostril three times a day

DRUGFlonase

daily nasal steroid sprays (Flonase, 2 sprays each nostril daily).

DRUGsugar pill

placebo pill to match doxycycline

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Nasal polyps on nasal endoscopy. * The patient has moderate to severe disease, defined by moderate to severe subjective symptoms (a score greater than 3 on a 10-cm VAS). * The patient is at least 18 years old. * The patient is able to understand and give informed consent. * The patient has clinically diagnosed chronic rhinosinusitis with nasal polyps according to the AAO-HNS diagnostic criteria: At least 2 of the following symptoms/signs: * Mucopurulent drainage (anterior, posterior, or both) * Nasal obstruction (congestion) * Facial pain-pressure-fullness * Decreased sense of smell * and symptoms lasting 12 weeks or longer.

Exclusion criteria

* The patient has a history of treatment with oral corticosteroids in the past 4 weeks. , * The patient has cystic fibrosis. * The patient has primary ciliary dyskinesia. * The patient has diabetes. * The patient has had sinus surgery in the past 3 months. * The patient has an allergy to doxycycline or related tetracyclines or glucocorticoids. * The patient is a minor. * The patient is a prisoner. * The patient has a psychiatric illness or developmental delay, which would interfere with understanding of the study and provision of informed consent. * The patient is a breastfeeding mother. The effects of the drugs used in this study (doxycycline) on breast milk are unknown and thus, these patients will be excluded from the study * The patient has a history of HIV or other known cause of immunosuppression, or is actively taking immunosuppressive medications due to organ transplantation, rheumatoid disease, or other medical conditions. * The patient is on penicillin; antacids containing aluminum, calcium, magnesium, or iron; bismuth subsalicylate; barbiturates; carbamazepine; and phenytoin; as well as tetracycline and Penthane. * Pregnancy. Doxycycline, a tetracycline, is a known teratogen. For this reason women of child-bearing potential are suggested to take a form of contraception for the duration that they are taking doxycycline., Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Pregnancy Testing. Women of childbearing potential are required to have a negative serum pregnancy test (with a sensitivity of at least 25 mIU/mL) prior to the first dose of drug. No further pregnancy tests are required since after this visit the patient will no longer be taking tetracycline after 3 weeks. Women of childbearing potential are defined as follows: * Patients with regular menses * Patients with amenorrhea, irregular cycles, or using a contraceptive method that precludes withdrawal bleeding * Women who have had a tubal ligation Women are considered not to be of childbearing potential for the following reasons: * The patient has undergone hysterectomy and/or bilateral oophorectomy. * The patient is post-menopausal defined by amenorrhea for at least 1 year in a woman \> 45 years old.

Design outcomes

Primary

Measure	Time frame	Description
Sino-nasal Outcome Test (SNOT 22)	Baseline and 12 weeks	a validated 22 item quality of life questionnaire for patients with chronic rhinosinusitis. Range of 0 to 110, higher scores indicate worse outcome

Secondary

Measure	Time frame	Description
Endoscopic Nasal Polyp Score	Baseline and 12 weeks	0- Absence of nasal polyps 1. Polyps confined to the middle meatus and not beyond the inferior border of the middle turbinate 2. Polyps reaching below the lower border of the middle turbinate 3. Large polyps extending to the lower border of the inferior turbinate or medial to the middle turbinate 4. Large polyps extending to the lower border of the inferior turbinate or medial to the middle turbinate Nasal polyp scores. The score is determined for each nostril, and the two scores added for a total nasal polyp score. Range of 0 to 8, graded on a size system from 0 to 4 and summed from the right and left nostrils.
Middle Meatus Culture	Baseline and 12 weeks	Culture swab for the presence or absence of microbial growth
Subjective Symptom Composite Scoring	Baseline and 12 weeks	A subjective symptom score will be extracted from the patient's score (on a scale of 0-5, where 0 defines no problems with the given symptom and 5 defines maximal problems ) on the SNOT-22 for each fo the following symptoms: blockage/congestion, runny nose, post-nasal discharge, facial pain/pressure, and sense of taste/smell. Range of 0 to 25, with higher score reflecting worse symptoms.
Visual Analog Scale	Baseline and 12 weeks	The visual analog scale for overall symptoms will be used to define disease severity. Range of 0 to 10. As per the European Position Paper 2012, mild, moderate, and severe disease will be defined as 0 to and including 3, \> 3 to and including 7, and \> 7 to and including 10, respectively.

Countries

United States

Participant flow

Recruitment details

Subjects were recruited from September 2014 to April 2016 at the Mount Sinai Department of Otolaryngology-Head & Neck Surgery rhinology practice.

Participants by arm

Arm	Count
Doxycycline Doxycycline plus oral methylprednisolone and nasal saline sprays	24
Sugar Pill placebo pill plus oral methylprednisolone for three weeks. After this, maintenance therapy which includes nasal saline sprays and daily nasal steroid sprays.	25
Total	49

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Lost to Follow-up	12	14

Baseline characteristics

Characteristic	Doxycycline	Sugar Pill	Total
Age, Continuous	51.5 years STANDARD_DEVIATION 13.8	44.1 years STANDARD_DEVIATION 12.2	47.7 years STANDARD_DEVIATION 13.4
Number of Participants with Prior Endoscopic Sinus Surgery (ESS)	13 Participants	13 Participants	26 Participants
Sex: Female, Male Female	10 Participants	13 Participants	23 Participants
Sex: Female, Male Male	14 Participants	12 Participants	26 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 24	0 / 25
other Total, other adverse events	0 / 24	0 / 25
serious Total, serious adverse events	0 / 24	0 / 25

Outcome results

Primary

Sino-nasal Outcome Test (SNOT 22)

a validated 22 item quality of life questionnaire for patients with chronic rhinosinusitis. Range of 0 to 110, higher scores indicate worse outcome