Osteonecrosis Due to Drugs, JawDrugHolidayNCT04540601
Antiresorptive Drug Continuation Compared With Drug Holiday in Cancer Patients Needing Tooth Extraction
A study testing Continuation of antiresorptives in relation to tooth extraction (surgical tooth removal) in people with Osteonecrosis Due to Drugs, Jaw, run by University of Copenhagen at 2 sites in Denmark.
Trial summary
The aim of this trial is to evaluate high-dose antiresorptive drug holiday related to tooth extraction with primary mucosal closure (surgical extraction) including how a drug holiday affects the health related quality of life. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Osteonecrosis Due to Drugs, Jaw
- What is being tested?
- Continuation of antiresorptives in relation to tooth extraction (surgical tooth removal)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 2 sitesDenmark
- Study dates
- 10 Jul 2018to 19 Aug 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients eligible for the trial must comply with all of the following at randomization:
- Patients aged 18 years or older.
- Patients with malignant disease (breast or prostate cancer, multiple myeloma) and metastases to the skeleton.
- Patients present high dose/intravenous antiresorptive therapy for at least 1 month.
- Patients who need tooth extraction. Indications for extraction include root fracture, endodontic failure, severe periodontal disease, non-restorable caries and teeth with a poor prognosis or at high risk of infection, complications.
- Patients who have an ECOG (Eastern Cooperative Oncology Group) score < 2 (30). Definition of ECOG 0. Fully active, able to carry on all pre-disease performance without restriction.
Show all 11Show fewer
- Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature e.g., light house work, office work.
- Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of walking hours.
- Capable of only limited selfcare, confined to bed or chair more than 50% of walking hours.
- Completely disabled. Cannot carry on selfcare. Totally confined to bed or chair.
- Signed informed content.
Who cannot join
- Patients must not have received radiation therapy to the jaws.
- Patients must not have exposed bone, or signs of non-exposed bone.
- Patients previous diagnosed with ONJ.
- Patients who are unable to cooperate or too ill to complete the experiment.
- Lack of signed informed consent.
Trial locations and contacts
2 sites in 1 country.
Denmark2 sites
Copenhagen University Hospital
Copenhagen, Copenhagen Ø, 2100
University of Copenhagen, Department of Odontology
Copenhagen, Nørrebro, 2200
About this study
Official title: Antiresorptive Drug Continuation Compared With Drug Holiday in Cancer Patients Needing Tooth Extraction - A Randomized Clinical Trial
The aim of this trial is to evaluate high-dose antiresorptive drug holiday related to tooth extraction with primary mucosal closure (surgical extraction) including how a drug holiday affects the health related quality of life.
Research question: Does a drug holiday have any influence on health related quality of life or the incidence of developing osteonecrosis of the jaw after surgical tooth extraction? The investigators hypothesize that a drug holiday 1 month before to 3 months after surgical tooth extraction in cancer patients do not influence the development of osteonecrosis of the jaw and may even affect the health related quality of life negatively.
Read the detailed description
Osteonecrosis of the jaw is a known adverse reaction to antiresorptive medication, including bisphosphonate and denosumab. The globally accepted term is Medication-Related Osteonecrosis of the Jaws (MRONJ). Since 2003 there has been a worldwide focus at medication-related osteonecrosis, even though there still exist several of unanswered questions - one of them is the effect of a drug holiday in relation to tooth extraction. A drug holiday is a temporary discontinuation of a drug and has been suggested among risk reduction strategies in the literature. It is still unknown whether a drug holiday plays a significant role in relation to tooth extraction for the development of osteonecrosis. The investigators want to investigate the importance of an antiresorptive drug holiday (bisphosphonate, denosumab) in relation to tooth extraction.
The aim of this trial is therefore to clarify the meaning of high-dose antiresorptive drug holiday related to tooth extraction with primary mucosal closure in cancer patients and reveal how a drug holiday affects the health related quality of life. A continuation of the patients' antiresorptive treatment can possibly lead to increased risk of osteonecrosis of the jaw, but with the operation procedure with primary closure it is unlikely. It is beneficial for the cancer patients to continue the high dose antiresorptive therapy because a drug holiday is a stop in their anti-cancer treatment with risk of increased pain as well as unwanted skeletal events to occur, and potentially progress of metastases to follow.
- Conditions
- Osteonecrosis Due to Drugs, Jaw
- Being tested
- Continuation of antiresorptives in relation to tooth extraction (surgical tooth removal)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Continuation of antiresorptives in relation to tooth extraction (surgical tooth removal)Other
We want to investigate the importance of an antiresorptive drug holiday (bisphosphonate, denosumab) in relation to tooth extraction. The experimental intervention in this trial is drug continuation starting before tooth extraction with primary closure.
We simply ask the participating cancer patients to continue their high dose antiresorptive treatment for 4 months (intervention-period: 1 month pre-operative, 3 months post-operative) instead of taking a drug holiday.
| Study group | Role | What they receive |
|---|---|---|
| Cancer patients, randomized A | Active comparator | Patients in high-dose antiresorptives with bone metastases Receives: Other: Continuation of antiresorptives in relation to tooth extraction (surgical tooth removal) |
| Cancer patients, randomized B | No intervention | Drug Holiday as standard operation procedure |
What is being measured
The primary outcome is the main question the study is designed to answer.
Development of osteonecrosis of the jaw (ONJ) or incomplete healing at 3 months follow-up
The outcome assessor has 3 options for registration related to ONJ occurrence:
- Complete healing = mucosal covering = no sign of ONJ, defined as complete wound healing; Intact mucosa, that is total mucosal covering over the tooth extraction area.
- Incomplete healing = presence of fibrin covering partly or over all mucosal operation area; Defined as the presence of fibrin at the surface of the operation area, thus still being a wound.
- ONJ present, defined according to the AAOMS position paper 2014 (4), all three items have to be present:
- Current or previous treatment with antiresorptive agents.
- Exposed bone or bone that can be probed through an extraoral or intraoral fistula that has persisted for longer than 8 weeks.
- No history of radiation therapy to the jaws or obvious metastatic disease to the jaws.
Measured: 3 months follow-up
EQ-5D-5L: Change in patients health related quality of life from allocation/enrollment
The patients are given the EQ-5D-5L questionnaire. The 5-level EQ-5D version (EQ-%D-5L) was introduced by the EuroQol Group in 2009 and consists of two pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, serve problems and extreme problems. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. The Danish dataset (SPSS syntax crosswalk values EQ-5D-5L Denmark) will be used to analyze patients´ responses.
Measured: The patient will be asked to fulfill the EQ-5D-5L at allocation/enrollment and again at 1, 3 and 6 months follow-up.
Secondary outcomes (3)
Pain from the jaw
Pain from the jaw is registered by a Visual Analogue Scale (VAS). The investigator will give the patient a paper with a VAS, see attached appendix 3, and ask following question: "On a scale from 0 to 10, where 0 is no pain and 10 is the worst thinkable pain, mark at the scale how much pain you feel from your jaw at tooth operation site".
Measured: This is asked prior to tooth extraction (time 0), at suture removal (time 10-14 days), at 1-month follow-up and at 3 and 6 months follow-up and is registered in the datasheet.
Incidence of unwanted skeletal events
The patient is giving a simple questionnaire, where they have to answer yes or no to following question: "Have you visited your own doctor or been hospitalized because of fractures or other skeletal complications during this trial period - yes or no. If yes, please write why." See attached appendix 4: Skeletal-related event questionnaire
Measured: Incidence (number of) unwanted skeletal events during the period and is registered at 3 and 6 months follow-up.
Progression of cancer disease
The tumor-evaluation will be done by the oncologic doctor in due to their departments routine.
Measured: The patient will be weighted at baseline, time of tooth removal, 1 month follow-up, 3 and 6 months follow-up visit.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2020
- Study start10 Jul 2018
- Primary completion1 Aug 2019
- Study completion19 Aug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Osteonecrosis Due to Drugs, JawStudies of the same condition, open and under way.
- More trials run by University of CopenhagenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This trial is designed as an investigator-initiated, parallel-group, randomized, clinical, single-blinded, trial investigating no antiresorptive drug holiday starting before tooth extraction with primary closure versus antiresorptive drug holiday starting before tooth extraction with primary closure in cancer patients
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Copenhagen
- Sponsor type
- University, hospital or other
- Collaborators
- Department of Oral and Maxillofacial Surgery, Copenhagen University Hospital
- Responsible party
- Principal investigator, Camilla Ottesen, University of Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04540601
- Sponsor's protocol ID
- H-18007990
- Acronym
- DrugHoliday
- Status last verified
- Sep 2020
- First submitted
- 24 Aug 2020
- Last updated
- 10 Sep 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Antiresorptive Drug Continuation Compared With Drug Holiday in Cancer Patients Needing Tooth Extraction - A Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT04540601
- Acronym / sponsor ID
- DrugHoliday / H-18007990
- Conditions
- Osteonecrosis Due to Drugs, Jaw
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University of CopenhagenUniversity, hospital or other
- Collaborators
- Department of Oral and Maxillofacial Surgery, Copenhagen University Hospital
- Study start
- 10 Jul 2018 (actual)
- Primary completion
- 1 Aug 2019 (actual)
- Study completion
- 19 Aug 2020 (actual)
- First posted
- 7 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this trial is to evaluate high-dose antiresorptive drug holiday related to tooth extraction with primary mucosal closure (surgical extraction) including how a drug holiday affects the health related quality of life.
Research question: Does a drug holiday have any influence on health related quality of life or the incidence of developing osteonecrosis of the jaw after surgical tooth extraction? The investigators hypothesize that a drug holiday 1 month before to 3 months after surgical tooth extraction in cancer patients do not influence the development of osteonecrosis of the jaw and may even affect the health related quality of life negatively.
Detailed description
Osteonecrosis of the jaw is a known adverse reaction to antiresorptive medication, including bisphosphonate and denosumab. The globally accepted term is Medication-Related Osteonecrosis of the Jaws (MRONJ). Since 2003 there has been a worldwide focus at medication-related osteonecrosis, even though there still exist several of unanswered questions - one of them is the effect of a drug holiday in relation to tooth extraction. A drug holiday is a temporary discontinuation of a drug and has been suggested among risk reduction strategies in the literature. It is still unknown whether a drug holiday plays a significant role in relation to tooth extraction for the development of osteonecrosis. The investigators want to investigate the importance of an antiresorptive drug holiday (bisphosphonate, denosumab) in relation to tooth extraction.
The aim of this trial is therefore to clarify the meaning of high-dose antiresorptive drug holiday related to tooth extraction with primary mucosal closure in cancer patients and reveal how a drug holiday affects the health related quality of life. A continuation of the patients' antiresorptive treatment can possibly lead to increased risk of osteonecrosis of the jaw, but with the operation procedure with primary closure it is unlikely. It is beneficial for the cancer patients to continue the high dose antiresorptive therapy because a drug holiday is a stop in their anti-cancer treatment with risk of increased pain as well as unwanted skeletal events to occur, and potentially progress of metastases to follow.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- This trial is designed as an investigator-initiated, parallel-group, randomized, clinical, single-blinded, trial investigating no antiresorptive drug holiday starting before tooth extraction with primary closure versus antiresorptive drug holiday starting before tooth extraction with primary closure in cancer patients
| Arm | Type | Receives |
|---|---|---|
| Cancer patients, randomized A | Active comparator | Other: Continuation of antiresorptives in relation to tooth extraction (surgical tooth removal)Patients in high-dose antiresorptives with bone metastases |
| Cancer patients, randomized B | No intervention | –Drug Holiday as standard operation procedure |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- Patients eligible for the trial must comply with all of the following at randomization:
- Patients aged 18 years or older.
- Patients with malignant disease (breast or prostate cancer, multiple myeloma) and metastases to the skeleton.
- Patients present high dose/intravenous antiresorptive therapy for at least 1 month.
- Patients who need tooth extraction. Indications for extraction include root fracture, endodontic failure, severe periodontal disease, non-restorable caries and teeth with a poor prognosis or at high risk of infection, complications.
Key exclusion criteria (5 listed)
- Patients must not have received radiation therapy to the jaws.
- Patients must not have exposed bone, or signs of non-exposed bone.
- Patients previous diagnosed with ONJ.
- Patients who are unable to cooperate or too ill to complete the experiment.
- Lack of signed informed consent.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Continuation of antiresorptives in relation to tooth extraction (surgical tooth removal)We want to investigate the importance of an antiresorptive drug holiday (bisphosphonate, denosumab) in relation to tooth extraction. The experimental intervention in this trial is drug continuation starting before tooth extraction with primary closure. We simply ask the participating cancer patients to continue their high dose antiresorptive treatment for 4 months (intervention-period: 1 month pre-operative, 3 months post-operative) instead of taking a drug holiday. | Other | Cancer patients, randomized A |
Primary outcome
Development of osteonecrosis of the jaw (ONJ) or incomplete healing at 3 months follow-up
Time frame: 3 months follow-up
The outcome assessor has 3 options for registration related to ONJ occurrence: * Complete healing = mucosal covering = no sign of ONJ, defined as complete wound healing; Intact mucosa, that is total mucosal covering over the tooth extraction area. * Incomplete healing = presence of fibrin covering partly or over all mucosal operation area; Defined as the presence of fibrin at the surface of the operation area, thus still being a wound. * ONJ present, defined according to the AAOMS position paper 2014 (4), all three items have to be present: 1. Current or previous treatment with antiresorptive agents. 2. Exposed bone or bone that can be probed through an extraoral or intraoral fistula that has persisted for longer than 8 weeks. 3. No history of radiation therapy to the jaws or obvious metastatic disease to the jaws.
EQ-5D-5L: Change in patients health related quality of life from allocation/enrollment
Time frame: The patient will be asked to fulfill the EQ-5D-5L at allocation/enrollment and again at 1, 3 and 6 months follow-up.
The patients are given the EQ-5D-5L questionnaire. The 5-level EQ-5D version (EQ-%D-5L) was introduced by the EuroQol Group in 2009 and consists of two pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, serve problems and extreme problems. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. The Danish dataset (SPSS syntax crosswalk values EQ-5D-5L Denmark) will be used to analyze patients´ responses.
3 secondary outcomes
Pain from the jaw
Time frame: This is asked prior to tooth extraction (time 0), at suture removal (time 10-14 days), at 1-month follow-up and at 3 and 6 months follow-up and is registered in the datasheet.
Incidence of unwanted skeletal events
Time frame: Incidence (number of) unwanted skeletal events during the period and is registered at 3 and 6 months follow-up.
Progression of cancer disease
Time frame: The patient will be weighted at baseline, time of tooth removal, 1 month follow-up, 3 and 6 months follow-up visit.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2020.
- Individual participant dataSharing planned: No
Related trials for Osteonecrosis Due to Drugs, Jaw
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Piezoeletric Surgery vs Conventional Surgery for Treatment of MRONJ
Bisphosphonate-Associated Osteonecrosis of the Jaw, Osteonecrosis of the Jaw
RecruitingObservational study
Medication Related Osteonecrosis of the Jaws (MRONJ) in a Cohort of Patients Treated by Antiresorptive Drugs
Osteonecrosis of the Jaw, Osteonecrosis Due to Drugs, Jaw
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Continuation of antiresorptives in relation to tooth extraction (surgical tooth removal) in people with Osteonecrosis Due to Drugs, Jaw, run by University of Copenhagen at 2 sites in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Development of osteonecrosis of the jaw (ONJ) or incomplete healing at 3 months follow-up (time frame: 3 months follow-up). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2020.