Vaginal Prednisone Administration for Prevention of Adrenal Crisis (Vapreda)
Primary Purpose
Adrenal Insufficiency
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
100mg prednisone suppository
Sponsored by
About this trial
This is an interventional prevention trial for Adrenal Insufficiency focused on measuring addison disease, adrenal crisis, prednisone
Eligibility Criteria
Inclusion Criteria:
- Female patients with chronic primary adrenal insufficiency due to autoimmune adrenalitis or bilateral adrenalectomy (disease duration at least 6 months)
- Age ≥ 18 years
- Patient´s written informed consent
- Ability to comply with the protocol procedures
- Established stable replacement therapy, no anticipated change in medication
- Negative pregnancy test and contraception (besides oral contraceptive pill) in pre-menopausal females
Exclusion Criteria:
- Diabetes mellitus
- Infectious disease with fever at time of investigation
- Known intolerance to the study drug or constituents
- Oral contraception
- Pregnancy or breast feeding
- Renal failure (creatinine >2.5 ULN)
- Disposition to vaginal mycosis (requiring treatment in the last 6 months or of necessity >2 antimycotic therapies/year)
- Recurrent urinary tract infections (of necessity >2 antibiosis therapies/year)
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Other
Other
Arm Label
vaginal administration first
rectal administration first
Arm Description
Intervention first visit: vaginal administration of 100mg prednisone suppository, Intervention second visit: rectal administration of 100mg prednisone suppository
Intervention first visit: rectal administration of 100mg prednisone suppository, Intervention second visit: vaginal administration 100mg prednisone suppository
Outcomes
Primary Outcome Measures
Bioequivalence of vaginal prednisone administration compared to rectal application, assessed by repeated determination of prednisolon levels (in blood)
The hypothesis is that the same prednisolone levels can be achieved within the same time frame after vaginale administration compared to rectal application.
Secondary Outcome Measures
Safety of the vaginal administration of prednisone compared to rectal application, assessed by the number of participants with treatment-related adverse events (using the NCI-CTC, version 4.0).
Suppressive effects on ACTH levels after vaginal administration of prednisone compared to rectal application, assessed by repeated determination of ACTH-levels
ACTH-levels are measured in plasma
Tolerability by the patients assessed by a questionnaire
Questions record the preference of the patients between vaginal and rectal application.
Full Information
NCT ID
NCT02689960
First Posted
February 8, 2016
Last Updated
June 19, 2017
Sponsor
Wuerzburg University Hospital
1. Study Identification
Unique Protocol Identification Number
NCT02689960
Brief Title
Vaginal Prednisone Administration for Prevention of Adrenal Crisis
Acronym
Vapreda
Official Title
Vaginal Prednisone Administration for Prevention of Adrenal Crisis - a Bioequivalence Study
Study Type
Interventional
2. Study Status
Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
January 2017 (Actual)
Primary Completion Date
April 2017 (Actual)
Study Completion Date
June 1, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Wuerzburg University Hospital
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Patients with chronic adrenal insufficiency need to adapt their glucocorticoid replacement dose in conditions of physical or psychological stress to prevent life threatening adrenal crisis. In cases of more severe impairment or unsecure gastrointestinal absorption (e.g. gastroenteritis, severe infectious disease), rapid and highly dosed administration of glucocorticoids is crucial. The study is conducted to offer female patients the possibility to perform efficient prednisone self-administration in emergency situations in a way of administration, which is easy to perform and accepted by the patients. Therefore, pharmacokinetics and safety of vaginal prednisone administration will be studied and compared to rectal administration.
Detailed Description
As patients with adrenal insufficiency still die from adrenal crisis, improvement of both prevention and also emergency management is needed. It is clear that perfect equipment and education of patients is key for further crisis prevention and management. Vaginal administration of prednisone-suppositories is easy to perform and independent of the gastro-intestinal system. Thus, this study aims at the efficacy, feasibility and safety of vaginal administration of prednisone-suppositories.
Recruitment:
Patients with primary adrenal insufficiency will be recruited. The adrenal insufficiency registry of Würzburg comprises more than 150 patients with primary adrenal insufficiency. Several patients have already indicated their interest to participate in the study. According to the European Medicines Agency (EMA) notes for guidance on the investigation of bioavailability and bioequivalence the number of 12 participants is regarded as the minimum required number.
Trial flow:
Pharmacokinetic studies will be performed at two different study visits. Patients will receive a 100mg prednisone suppository (Rectodelt® 100 mg) vaginal and rectal on two different study visits (interval longer then one week). Blood samples for determination of prednisone and adrenocorticotropic Hormone (ACTH) levels will be collected over a time period of 6 hours. Patients receive a diary to document eventual local or systemic adverse events during the following 7 days.
Stopping rules:
Participation of patients is fully voluntarily. Patients are able to stop participation in the study at any point in time. In addition, patients might claim the elimination of all data material at any point in time. Furthermore, study participation will be stopped for the individual patient, if new safety issues occur (e. g. new diagnosis of Diabetes mellitus, pregnancy or acute infectious disease) during the study. Relevant risks to the patients are highly unlikely. However, if 2 or more patients experience serious adverse events associated with the vaginal administration of prednisone with high likelihood, the study will be stopped.
Written informed consent:
A consent document including patient information upon the nature, scope and possible consequence of the trial must have been approved by the Institutional Review Board. Patients amenable for inclusion in the trial will be given sufficient time to study the written information, as well as possibility to ask questions before signing the consent document.
Analysis:
Documentation and analysis will be performed at the Department of Medicine I, Endocrine and Diabetes Unit, University of Würzburg, Germany. Data will be documented after pseudonymisation in a data base. Data analysis is mainly descriptive (bioequivalence of vaginal prednisone administration compared to rectal application, estimation of the patients regarding convenience and tolerability of different modes of drug administration, safety aspects).
Safety:
In the course of the trial, changes in physical findings as well as clinical signs and symptoms that may reflect adverse effects will be documented. Furthermore, all adverse events will be documented on the appropriate report form. When an adverse event occurs it will be graded according to the National cancer Institute - common toxicity criteria (NCI-CTC) (version 4.0). Patients receive a diary to document any local or systemic adverse event during the following 7 days after intervention. In addition, patients will be contacted by phone 3(±1) and 7(±1) days after vaginal administration of prednisone. If patients report any adverse events that are possibly related to the vaginal administration route, they will be called-in for further physical examination and detailed documentation. To further enhance individual patient's safety during the study, a safety assessment will be performed prior to the subsequent intervention. In addition, a safety assessment will be performed after 4 and 8 subsequent vaginal administrations of prednisone with evaluation of events during the 7 day follow up period after administration.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adrenal Insufficiency
Keywords
addison disease, adrenal crisis, prednisone
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
vaginal administration first
Arm Type
Other
Arm Description
Intervention first visit: vaginal administration of 100mg prednisone suppository, Intervention second visit: rectal administration of 100mg prednisone suppository
Arm Title
rectal administration first
Arm Type
Other
Arm Description
Intervention first visit: rectal administration of 100mg prednisone suppository, Intervention second visit: vaginal administration 100mg prednisone suppository
Intervention Type
Drug
Intervention Name(s)
100mg prednisone suppository
Other Intervention Name(s)
Rectodelt (approval number 6329964.00.00)
Intervention Description
vaginal administration of 100mg prednisone suppository (Rectodelt)
Primary Outcome Measure Information:
Title
Bioequivalence of vaginal prednisone administration compared to rectal application, assessed by repeated determination of prednisolon levels (in blood)
Description
The hypothesis is that the same prednisolone levels can be achieved within the same time frame after vaginale administration compared to rectal application.
Time Frame
up to 12 months
Secondary Outcome Measure Information:
Title
Safety of the vaginal administration of prednisone compared to rectal application, assessed by the number of participants with treatment-related adverse events (using the NCI-CTC, version 4.0).
Time Frame
up to 12 months
Title
Suppressive effects on ACTH levels after vaginal administration of prednisone compared to rectal application, assessed by repeated determination of ACTH-levels
Description
ACTH-levels are measured in plasma
Time Frame
up to 1 week
Title
Tolerability by the patients assessed by a questionnaire
Description
Questions record the preference of the patients between vaginal and rectal application.
Time Frame
up to 1 month
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Female patients with chronic primary adrenal insufficiency due to autoimmune adrenalitis or bilateral adrenalectomy (disease duration at least 6 months)
Age ≥ 18 years
Patient´s written informed consent
Ability to comply with the protocol procedures
Established stable replacement therapy, no anticipated change in medication
Negative pregnancy test and contraception (besides oral contraceptive pill) in pre-menopausal females
Exclusion Criteria:
Diabetes mellitus
Infectious disease with fever at time of investigation
Known intolerance to the study drug or constituents
Oral contraception
Pregnancy or breast feeding
Renal failure (creatinine >2.5 ULN)
Disposition to vaginal mycosis (requiring treatment in the last 6 months or of necessity >2 antimycotic therapies/year)
Recurrent urinary tract infections (of necessity >2 antibiosis therapies/year)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stefanie Hahner, MD, Prof.
Organizational Affiliation
University Hospital Wuerzburg
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
Yes
Citations:
PubMed Identifier
25419882
Citation
Hahner S, Spinnler C, Fassnacht M, Burger-Stritt S, Lang K, Milovanovic D, Beuschlein F, Willenberg HS, Quinkler M, Allolio B. High incidence of adrenal crisis in educated patients with chronic adrenal insufficiency: a prospective study. J Clin Endocrinol Metab. 2015 Feb;100(2):407-16. doi: 10.1210/jc.2014-3191. Epub 2014 Nov 24.
Results Reference
background
PubMed Identifier
25200922
Citation
Hahner S, Hemmelmann N, Quinkler M, Beuschlein F, Spinnler C, Allolio B. Timelines in the management of adrenal crisis - targets, limits and reality. Clin Endocrinol (Oxf). 2015 Apr;82(4):497-502. doi: 10.1111/cen.12609. Epub 2014 Nov 6.
Results Reference
background
PubMed Identifier
19955259
Citation
Hahner S, Loeffler M, Bleicken B, Drechsler C, Milovanovic D, Fassnacht M, Ventz M, Quinkler M, Allolio B. Epidemiology of adrenal crisis in chronic adrenal insufficiency: the need for new prevention strategies. Eur J Endocrinol. 2010 Mar;162(3):597-602. doi: 10.1530/EJE-09-0884. Epub 2009 Dec 2.
Results Reference
background
PubMed Identifier
23672956
Citation
Hahner S, Burger-Stritt S, Allolio B. Subcutaneous hydrocortisone administration for emergency use in adrenal insufficiency. Eur J Endocrinol. 2013 Jun 29;169(2):147-54. doi: 10.1530/EJE-12-1057. Print 2013 Aug.
Results Reference
background
PubMed Identifier
25288693
Citation
Allolio B. Extensive expertise in endocrinology. Adrenal crisis. Eur J Endocrinol. 2015 Mar;172(3):R115-24. doi: 10.1530/EJE-14-0824. Epub 2014 Oct 6.
Results Reference
background
PubMed Identifier
26208266
Citation
Smans LC, Van der Valk ES, Hermus AR, Zelissen PM. Incidence of adrenal crisis in patients with adrenal insufficiency. Clin Endocrinol (Oxf). 2016 Jan;84(1):17-22. doi: 10.1111/cen.12865. Epub 2015 Aug 27.
Results Reference
background
PubMed Identifier
12151163
Citation
Anderson M, Kutzner S, Kaufman RH. Treatment of vulvovaginal lichen planus with vaginal hydrocortisone suppositories. Obstet Gynecol. 2002 Aug;100(2):359-62. doi: 10.1016/s0029-7844(02)02117-8.
Results Reference
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Vaginal Prednisone Administration for Prevention of Adrenal Crisis
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