Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04097613 |
| Other study ID # |
H17-01373 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Early Phase 1
|
| First received |
|
| Last updated |
|
| Start date |
July 28, 2017 |
| Est. completion date |
August 31, 2019 |
Study information
| Verified date |
September 2019 |
| Source |
St. Paul's Hospital, Canada |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Povidone Iodine solution is a nasal antiseptic. Its application has been shown to be
clinically safe, tolerable and effective against bacteria and fungi associated with chronic
rhinosinusitis.
This study will evaluate the effectiveness of Povidone Iodine in this hard-to-treat patient
group. Furthermore, the study will also further evaluate any side effects that may occur with
the use of Povidone Iodine.
Description:
Background and scientific rationale Chronic rhinosinusitis (CRS) is an inflammatory condition
of the paranasal sinuses affecting millions of patients, resulting in billions of dollars
being spent annually in associated health care costs. Biofilm has been implicated in chronic
rhinosinusitis recalcitrant to appropriate medical therapy and well-executed endoscopic sinus
surgery. The presence of biofilm results in patients having worse postoperative symptoms,
recurrent infections, and persistent inflammation. Biofilms are bacterial or fungi
communities surrounded by an extracellular polysaccharide matrix, which facilitates
attachment to mucosa, survival, protection and proliferation. This configuration allows for
resistance to innate host defenses and resistance to antibiotic therapy.
Povidone Iodine solution 5% (0.5% available iodine) by 3MTM has been specially formulated as
a nasal antiseptic. They have shown topical application to be clinically safe, tolerable and
to be rapidly bacteriocidal against aerobic gram positive and gram- negative bacteria
including methicillin resistant Staphylococcus aureus, methicillin resistant Staphylococcus
epidermidis, vancomycin resistant Enterococcus faecium and Enterococcus faecalis (VRE) and
yeast(3M study 05-011100,05-011017, 05-011322).
Iodine is the active antimicrobial component in PVP-I. It has potent bactericidal, fungicidal
and viricidal properties. It is an important element in the human body and is not known to be
an allergen. Therefore there are no true allergies to iodine but rare cases of intolerance.
In Japan, it is commonly recommended to gargle with PVP-Ito prevent upper respiratory
infections. A prospective study evaluating the effect of mouth rinsing on iodine absorption
and thyroid function showed that use of the mouthwash 4 times a day for 2 weeks or once a day
for 24 weeks did not affect thyroid function. An evidence based review of randomized
controlled trials and comparative studies determining the efficacy and risk associated with
PVP-I irrigations used in general surgery, cardiovascular surgery, urological surgery, and
orthopedic surgery found no significant risk were associated with the PVP-I irrigations other
than increasing serum iodine.
There is a paucity of published data on the use of iodine during or after sinus surgery to
treat biofilm. This study aims to determine if topical PVP-I rinses will result in an
improvement in disease severity as determined by endoscopic scores (Modified Lund-Kennedy
score). Secondly, as biofilm has been recognized as a source of poor outcomes in patients
with recalcitrant chronic sinusitis (CRS), the study aims to determine if there's a
significant reduction in biofilm biomass (bacterial or fungal) within the sinuses of
recalcitrant CRS patients. In addition, the study will evaluate if there is a significant
symptomatic improvement with the use of iodine rinses post-operatively.
Primary Objective:
To determine differences in Modified Lund-Kennedy (MLK) endoscopic score after 6 weeks of
using Povidone-iodine (PVP-I) sinus rinses.
Secondary Objectives:
1. To determine if the use of Povidone iodine (PVP-I) sinus rinses reduces the
number/density of biofilm colony forming units (bacterial or fungal) seen on mucosal
biopsy of the sinus with evidence of recalcitrant/recurrent chronic rhinosinusitis (CRS)
after 6 weeks.
2. To determine if the use of PVP-I sinus rinse improves disease specific quality of life
in recalcitrant/recurrent CRS patients.
Baseline Evaluation
The following information will be obtained from each participant
Demographic data:
Age Gender Smoking status
Clinical data:
Thyroid function test (TSH and FT3/FT4 levels if indicated) at baseline and 6 weeks
Eosinophil and Basophil levels Serum IgE levels Bacterial and fungal cultures (at
baseline and 6weeks) History of sinus surgery Smell test at baseline and 6 weeks
Saccharin test (Baseline and after 6 weeks)
Conduct of the Study:
Upon enrollment in the study, demographic data and clinical data will be obtained. The
patient will be asked to fill out a SNOT-22 questionnaire, endoscopic pictures will be
taken, culture taken via a suction trap and a biopsy of the sinus lining evidently
affected by biofilm. The biopsy is painless and does not usually require local
anesthesia but will be used if requested by the patient. A single bite of the mucosa is
taken to remove tissue approximately 1x1mm. Bleeding is temporary and resolves
spontaneously. Baseline smell test (University of Pennsylvania Smell Identification
Test) followed by a saccharin test is done. All of the above except for the saccharin
test and mucosal biopsy are a part of the routine clinical examination done for the
patients in the rhinology clinic. A saccharin test will be used to establish the
baseline cilia function, which is known to be denuded by biofilm13.
The biopsy will be examined for biofilm (density and type of colony forming units) by
scanning electron microscopy at the Centre for High-Throughput Phenogenomics at the
University of British Columbia (UBC), part of the UBC Imaging Labs27.
The patient will then be sent for baseline blood work (thyroid function test, IgE,
eosinophil and basophil levels) and instructed to rinse with PVP-I added to their
regular saline rinse. They will continue using the rinse for 6 weeks until they come
back for their follow-up visit.
Patients will then be seen 6 weeks later. They will be required to fill out the SNOT-22
questionnaire and would undergo endoscopic examination, smell and saccharin test. A
biopsy is then taken from an adjacent site to the one taken upon enrollment in the
study. They will then be sent for repeat eosinophil, basophil, IgE and TFTs levels. A
blood test is a normal part of the evaluation done for the rhinology patient. The
addition of the TFT will not require more injections for the patient.
Management of Patient Care
Patients have the right to withdraw from the study at any time. Patients who experience
signs and symptoms of hypersensitivity to iodine, burning, itching, pain redness,
tiredness, nausea or vomiting will be asked to stop the rinses immediately. The reaction
will be noted and the code will be broken so that a discussion can occur between the
physician and the patient regarding the use of iodine with the nasal rinses. Patients
who meet any of the exclusion criteria that were not noted at the beginning of the study
will be removed from this study and the physician will discuss the future management
options with the patient.
Drugs
Povidone Iodine (PVP-I)
Dosing and Administration
PVP-I is provided in the form of a liquid at a concentration of 10% (1% available
iodine). 2 mL of PVP-I will be diluted into 250 mL of saline solution. The final
concentration of available iodine in the solution would be 0.008%.
Dose Schedule:
Patient will dilute 2 mL of 10% iodine into a 250 mL rinse bottle once a day
Duration of therapy:
The patient will administer the PVP-I or Saline rinse for 6 weeks
Side effects
The literature has some isolated reports of adverse reactions to iodine administration
to include burning, swelling, and pain. No documented episode of anaphylaxis due to
iodine has been identified in the literature. There are reports of TSH suppression with
excessive mouth gargles with iodine, however, this is quickly reverses upon cessation of
use.
Budesonide
Dosing and Administration:
Budesonide is provided in nebules (1mg/2cc). Patients will place two nebules of
budesonide into the 250mls of saline
.
Dose Schedule:
Patients will administer the rinse once a day (2mg per day in total).
Duration of Therapy:
Patients will administer the budesonide for the entire duration of the study (42 days).
Side Effects:
Budesonide is generally well tolerated. The most common side-effect is drying of the
nose, which may lead to nose bleeds.
Inhaled budesonide may cause dysphonia, sore throat, and oralpharyngeal candidiasis.
Headaches, asthenia and pain have been attributed to inhale budesonide as well. There
are a number of ide effects which require consideration if topical budesonide reaches
similar plasma concentrations as oralbudesonide, which include: depression, aggression,
irritability, anxiety, psychosis, increased appetite, confusion, insomnia, nervousness,
sleep disorder, amnesia, somnolence, reduction in bone density, chest pain,
palpitations, tachycardia, dependent edema, facial edema, hypertension, flushing,
increased C-reactive protein, acne, alopecia, dermatitis, eczema, increased sweating and
skin disorders.
Sample Size:
Based on a retrospective study from our centre (St. Paul's Sinus Centre), that noted
change in MLK score for 69 patients who used PVP-I, we were able to calculate a sample
size for our prospective cohort study. 15 patients (30 sinus cavities) will be required
to have an 80% chance at detecting a statistically significant (p-value < 0.05) decrease
in MLK score. To account for a drop-out rate of 25% we plan to recruit 19 patients.
Analysis:
The primary outcome will be the change in MLK score before and after PVP-I use for 6
weeks. Secondary outcomes will be patient-reported quality of life (SNOT-22) and
difference in biofilm CFUs. Descriptive statistics (mean, median, SD) will be used to
describe demographic characteristics of the patients. The difference in MLK scores,
CFUs, and SNOT-22 before and after treatment within and between groups will be analyzed
using paired and unpaired students t-tests based on the variance of the outcomes.
Safety Monitoring
Patients who experience signs and symptoms of iodine reaction will be noted and the code
will be broken so that a discussion can occur between the research supervisor and the
patient regarding the use of the topical iodine.
Patients can contact the office anytime if they notice any of the signs or symptoms of
iodine reaction and will be seen by the research supervisor (or designate) within 24
hours.
Adverse Events (AE's)
All expected and unexpected adverse events will be recorded and graded by the research
supervisor. Stablechronic conditions, which are present prior to the clinical trial
entry and do not worsen, are not consideredadverse events and will be accounted for in
the patient's medical history.
Recording/Documentation of Adverse Events
During each patient visit, the research supervisor will ask appropriate questions and
perform a physical exam to elicit any adverse events. The research supervisor will also
review blood work obtained from the patient. All reportable adverse events will be
recorded on appropriate case report form. The research supervisor will also write the
stop date, the severity of the AE and his judgment of the AE's relationship to the
study.
Serious Adverse Events (SAE's)
An SAE is defined as an AE meeting one of the following:
- Death occurring between Day 0 and 42 of the study.
- Life Threatening Event (defined as a participant at immediate risk of death at the
time of the event)
- In-patient hospitalization or prolongation of existing hospitalization between Day
0 and 42 of the study.
- Results in a persistent or significant disability/incapacity
In the event of SAE, the research supervisor will discuss with the patient (or next of
kin) whether there is a relationship between the study and the SAE. If there is a
relationship, the PI will be responsible for coordinating care for the patient until the
SAE has been addressed.
Pregnancy During the Trial Patients will be responsible for determining if they are
pregnant or become pregnant during the study. If patients notify the PI they are
pregnant, they will be removed from the study and the medical management options will be
discussed.
