Octreotide VS Placebo in Prevention of Salivary Fistulae After Post Radiation Salvage Surgery

September 10, 2019 updated by: Hadassah Medical Organization

Prospective Randomized, Double-blind, Placebo-controlled Parallel Group Study of the Efficacy of Octreotide in Prevention of Salivary Fistulae After Post Radiation Salvage Surgery

Salivary fistulae have been the bane of surgical salvage in the era of primary chemoradiation for head and neck (H&N) cancers. The "blame"of prior chemoradiation tissue damage encouraged compensatory surgical techniques that focused on the insertion of non-irradiated tissue into the field. This study emphasizes a paradigm shift in the understanding and treatment of pharyngocutaneous fistulae. The detrimental effects of salivary enzymes on tissue healing and surgical anastomoses are addressed and novel treatment strategy is outlined.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

After signing an informed consent form, patients scheduled for total laryngectomy or for composite resections for oral/pharyngeal/laryngeal malignant tumors, will be randomly divided into two groups of about ten in each. The control group will receive a placebo while the study group will receive octreotide. All involved in the care of the patients and the patients themselves will be blinded to the drug given. The rest of the treatment will be equal in both groups and will adhere to the current departmental protocols in Otolaryngology/Oral-Maxillofacial Surgery.

The studied drug (Octreotide 100 mcg s/c) or placebo will be administered in the evening prior to surgery and subsequently for two weeks on a thrice daily basis.

Both groups will remain in hospital postoperatively for a minimum two week period (the current common practice). In addition to daily wound assessments, including daily grading of the pharyngocutaneous fistulae (using our grading system), the patients will also be evaluated for:

Serology:

  1. Complete blood count and biochemistry including CRP and amylase will be assessed every 3 days.
  2. GlucoChecks will be performed daily.

Imaging:

1. Patients will have an abdominal ultrasound to examine the gallbladder prior to and following completion of the two-weeks of therapy.

Admission stay:

Fistula prevention or acceleration of healing will be reflected in the admission time; generally, patients with fistulae suffer prolonged hospital stays.

Quality of Life Evaluation:

Evaluation of patients' quality of life will be based on two assessment scores:

  1. Pain evaluation:

    Patients will rate their average head and neck region pain intensity with a 0-10 Numeric Rating Scale (NRS) (comprising 11 integers including 0), where 0 is "no pain" and 10 represent "the worst pain possible". Assessment will include a record of 'current NRS '-representing current pain and 'NRS maximum' representing maximal recalled pain in the in the last six months. The NRS highly correlates to other pain assessment scales and is a valid, reliable and easy to use tool in clinical dental practice.

  2. Oral Health Impact Profile (OHIP-14) questionnaire:

The validated Hebrew version of the short OHIP (Oral Health Impact Profile) questionnaire (OHIP-14) will be used to assess the Oral health-related quality of life (OHRQoL). For each OHIP-14 question, subjects will be asked how frequently they had experienced the impact in the last six months. Responses will be made on a 5 point ordinal scale: 0-never , 1-hardly ever, 2-occasionally, 3- fairly often, and 4-very often. OHRQoL impairment will be characterized by the OHIP-14 global score, with a potential range of 0 (no adverse impacts within the last six months) to 56 (all 14 impacts experienced very often within the last six months). The OHIP-14 includes seven conceptual dimensions of oral health related quality of life. The dimensions are functional limitation, physical pain, psychological discomfort, physical disability, psychological disability, social disability and handicap. OHIP-14 domains will be calculated for each of the domains by summing the response scores for the two corresponding items. Relationships between OHIP-14 score and various socio-demographic parameters, health-related behaviors and pain scores will be assessed among the study population.

CBCT sialography:

On order to monitor the progression of the salivary gland healing process a cone beam computorized tomography (CBCT) sialography will be implemented.

Saliva collection and analysis:

Patients from the 2 groups will be asked not to eat, drink or brush their teeth an hour before saliva collection. Thereafter, the saliva secretion rate from the affected parotid gland (in the operative side) will be measured between 8 to 12 AM using the Carlson-Crittenden collector. Prior to placement of the cup, the buccal mucosa will be dried with gauze and the Stensen's ducts will be slightly squeezed to locate the ducts' orifices. Salivary flow will be stimulated with 2% citric acid. Saliva will be collected for a total time of 5 minutes. Samples will be kept on ice during and after saliva collection. Thereafter, samples will be centrifuged at 14,000 rpm for 20 min at 4°C. Supernatant will collected and protein concentration will be determined according to Bradford (Bio-Rad, Hercules, CA, USA). Several components secreted in saliva will be assessed including: Cortisolamylase, cytokines, growth factors, elastases and proteinases. Octreotide levels in saliva will also be assessed. In addition, sialochemical analysis of Na+, K+, Cl-, Ca2+, PO43-, Mg2+ concentrations will be performed.

Proteomic analysis:

Depending on protein concentrations further analysis may include supplementary characterization of salivary biomarkers including SDS-PAGE analysis, two-dimensional analytical gels, mass spectrometry identification and database searching.

Statistics Numerical variables will be presented as means and standard deviations, while categorized variables will be presented as frequencies and percentages. A Pearson's correlation coefficient method will be used. Differences between variables will be subjected to univariate analysis by t-test and ANOVA. The statistical processing will be established by SPSS 21.0. Statistical level of significance chosen as P < 0.05.

To examine the factors associated OHIP-14 total score in a multivariate model a conceptual hierarchical multiple regression model will be adopted within the uni-variate data7. This well-established approach employs sequential adjustments from distal to proximal determinants of a health condition, with the aim of elucidating their relationships. Conceptual analysis, contrary to statistical decisions on significant determinants of diseases, adopts a theoretical ordering. The ordering of variables is conceptually determined in accordance with the hypothesis which assumes which variables have confounding effects, and which variables have a modification effect.

Study Type

Interventional

Enrollment (Anticipated)

40

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Israel
      • Jerusalem, Israel
        • Recruiting
        • HadassahMO
        • Contact:
          • Jeff M

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Chemoradiation
  • Total laryngectomy
  • Composite resections for oral/pharyngeal/laryngeal malignant tumors

Exclusion Criteria:

  • Pregnancy
  • Patients with malabsorption syndrome, short bowel or chologenic diarrhea not controlled by specific therapeutic means
  • Patients with uncontrolled diabetes mellitus or a fasting plasma glucose > 250mg/d

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: octreotide treatment
The studied drug Octreotide 100 mcg will be administered I.V in the evening prior to surgery and for two weeks on a thrice daily basis.
Drug: octreotide
Octreotide has been in clinical use for thirty years and approved for use in Israel in acromegaly and functional gastroenteropancreatic tumours. It is currently being used extensively in surgical patients to prevent pancreatic fistulae1, and in lymphorrhea (both lymphatic malformations and leaks from the thoracic duct)
Other Names:
  • sundostatine
Placebo Comparator: placebo treatment
plasebo will be administrated I.V in the evening prior to surgery and two weeks on a thrice daily basis
Other: placebo
placebo ( saline) act as comperator in this study.
Other Names:
  • saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
elimination of post-radiation salivary fistulae
Time Frame: up to 7 days after the surgery
yes/no fistulae formation
up to 7 days after the surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
saliva secretion rate
Time Frame: up 14 days after the surgery
saliva collection
up 14 days after the surgery
pain evaluation
Time Frame: up to 14 days after the surgery
using of Numeric Rating Scale (NRS)
up to 14 days after the surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hadassah Medical Organization

Investigators

  • Principal Investigator: jeffrey weinberger, MD, Hadassah MO

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2015

Primary Completion (Anticipated)

June 1, 2021

Study Completion (Anticipated)

June 1, 2021

Study Registration Dates

First Submitted

April 29, 2015

First Submitted That Met QC Criteria

May 5, 2015

First Posted (Estimate)

May 8, 2015

Study Record Updates

Last Update Posted (Actual)

September 12, 2019

Last Update Submitted That Met QC Criteria

September 10, 2019

Last Verified

September 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0102-15-HMO-CTIL

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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