Injection Site VesiclesPhase 3PROTOTOXNCT00948103
The Interest of the Nitrous Oxide During Intravesical Injection of Botulinum Toxin A
A Phase 3 study testing Nitrous Oxide and Oxygen in people with Injection Site Vesicles, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Second line treatment for detrusor hyperreflexia is the intravesical BTX-A injections. First 300 units Botox are diluted with 30 ml of preservative-free saline. Using a rigid cystoscope and an injection needle, BTX-A is injected into 30 sites within the detrusor muscle. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Injection Site Vesicles
- What is being tested?
- Nitrous Oxide and Oxygen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 33 participants
- Where
- 1 siteFrance
- Study dates
- Sep 2008to Dec 2011
- Phase
- Phase 3
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Man or woman of more than 18 years
- Patient with overactive bladder
- First intravesical Botulinum injection
- Bladder sensitivity on the urodynamic
- Patient not presenting contraindication to this injection
- Cystoscopy realized before the injection of botulinal toxin A
- Negative pregnancy test for women of child-bearing age
- Signing of an informed consent form, after appropriate information has been provided
Who cannot join
- Pregnancy
- Contraindication in the toxin such as severe myasthenia, syndrome of Eaton-Lambert, or amyotrophic lateral sclerosis
- Treatment antibiotic by aminoglycoside
- Allergies known about the toxin, about the anesthetics used during the study
- Patients under anticoagulants, or having taken a treatment anti-aggregant platelet in 10 days preceding the injection
- Haemophilia or deficit in factor of the coagulation responsible for disorder of the haemostasis
Show all 25Show fewer
- Current urinary infection defined in the ECBU by a superior bacteriuria in 10°5 / ml and a leucocyturia superior to 10°4 / ml
- Current genital infection or in four weeks preceding the injection
- Histories of irradiation pelvic or treatment in the course of a neoplasia
- Current treatment or in six months preceding the randomisation by a pharmacological ENDOVESICAL agent
- Patients requiring a ventilation in pure oxygen
- Intra-cranial high blood pressure
- Conscience alteration
- Lung diseases
- Bubbles of emphysema
- Gaseous embolism
- Accident of dive
- Abdominal gaseous distension
- Patient having received recently an ophthalmic gas (SF6, C3F8, C2F6) used in the eye surgery as long as persists a bubble of gas inside the eye and at least during a period of 3 months
- Facial traumatism
- Chronic respiratory failure
- Analgesic treatment by morphine or morphine agonists of class 3
- Psychiatric pathology interfering with the compliance to the protocol or not allowing a correct evaluation of the result
- Patient having participated in a clinical study in 3 months preceding the inclusion
- No affiliation to any social insurance system
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Nitrous Oxide (KALINOX®) Inhalation and Tolerance of Intravesical Botulinum Neurotoxin A Injection: a Double-blind Randomized Controlled Study
Second line treatment for detrusor hyperreflexia is the intravesical BTX-A injections. First 300 units Botox are diluted with 30 ml of preservative-free saline. Using a rigid cystoscope and an injection needle, BTX-A is injected into 30 sites within the detrusor muscle.
The used of KALINOX® (50% nitrous oxide and oxygen) inhalation has demonstrated analgesic efficacy in various procedures (obstetric, liver biopsy, transrectal ultrasound guided prostate biopsy, emergency) The aim of this study is to investigate the safety and efficacy of analgesia with N2O/O2 inhalation for detrusor BTX-A injections using a rigid cystoscope.
Read the detailed description
First line treatment for detrusor hyperreflexia is the use of antimuscarinic medications. However, these medications can have unwanted side effects and often are not good enough to decrease incontinence in cases of severe neurogenic detrusor overactivity. Some invasive surgical procedures are possible such as sacral nerve stimulator, sacral rhizotomy, bladder myomectomy and bladder augmentation. But there are still few treatment option for this medical complication. Recently, some data are showed the clinical application of botulinum neurotoxin A (BTX-A) into detrusor muscle in cases of resistant neurogenic detrusor overactivity to conventional treatment with anticholinergic medication. In these studies the authors perform intravesical BTX-A injections. First 300 units Botox are diluted with 30 ml of preservative-free saline. Using a rigid cystoscope and an injection needle, BTX-A is injected into 30 sites within the detrusor muscle.
To reduce the pain, instillation of lidocaine before botulinum-A toxin injections is used into the bladder. On a 10-point rating scale the mean pain score of the patients who underwent the injections of Botox after conventional lidocaine instillation is 4.0 (SD 1.6).
The used of KALINOX® (50% nitrous oxide and oxygen) inhalation has demonstrated analgesic efficacy in various procedures (obstetric, liver biopsy, transrectal ultrasound guided prostate biopsy, emergency…) associated with mild to moderate pain and it is technically simple to use. Early studies indicated that 30% nitrous oxide is equipotent to 10 to 15 mg. morphine. Except in patients with severe chronic obstructive pulmonary disease KALINOX® inhalation is a safe and acceptable method of sedation and analgesia. It is a nonirritant and is excreted unchanged from the lungs.
The aim of this study is to investigate the safety and efficacy of analgesia with N2O/O2 inhalation for detrusor BTX-A injections using a rigid cystoscope. Will be included patient with severe neurogenic detrusor overactivity but with preserved bladder sensibility treated with botulinum-A toxin injections into the detrusor muscle Patients will be randomized into a group that will receive KALINOX® via a breath activated device and a control group that receive oxygen through a similar breathing device. The investigator will be involved in the randomization process since the gas cylinders will be covered and they will be blind to the gas used. All patients involved will be blinded to the gas that they will inhale. The patients will score the injection pain and the anxiety on a 10-point rating scale. Furthermore the duration of the practice will be measured.
The hypothesis is that analgesia with KALINOX® will show a significant difference in pain perception among the 2 groups.
- Conditions
- Injection Site Vesicles
- Being tested
- Nitrous Oxide, Oxygen
- Keywords
- Nitrous Oxide, Administration, Intravesical Drug, Botulinum toxin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nitrous OxideDrug
nitrous oxide inhalation during intravesical injection. Dose depends on gender and pain
OxygenDrug
oxygen
| Study group | Role | What they receive |
|---|---|---|
| Oxygen | Placebo comparator | Not described Receives: Drug: Oxygen |
| Nitrous Oxide | Active comparator | Not described Receives: Drug: Nitrous Oxide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean pain during intravesical injection
Measured: 5 minutes
Secondary outcomes (2)
Maximum pain during intravesical injection
Measured: 5 minutes
Anxiety during intravesical injection
Measured: 5 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2009 (estimated)
- Study startSep 2008
- Primary completionDec 2011
- Study completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Injection Site VesiclesStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pierre DENYS, PUPH, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00948103
- Sponsor's protocol ID
- P050701
- Acronym
- PROTOTOX
- Status last verified
- Nov 2014
- First submitted
- 28 Jul 2009
- Last updated
- 6 Nov 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nitrous Oxide (KALINOX®) Inhalation and Tolerance of Intravesical Botulinum Neurotoxin A Injection: a Double-blind Randomized Controlled Study
- ClinicalTrials.gov ID
- NCT00948103
- Acronym / sponsor ID
- PROTOTOX / P050701
- Conditions
- Injection Site Vesicles
- Keywords
- Nitrous Oxide, Administration, Intravesical Drug, Botulinum toxin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Sep 2008
- Primary completion
- Dec 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 29 Jul 2009 (estimated)
- 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.
Second line treatment for detrusor hyperreflexia is the intravesical BTX-A injections. First 300 units Botox are diluted with 30 ml of preservative-free saline. Using a rigid cystoscope and an injection needle, BTX-A is injected into 30 sites within the detrusor muscle.
The used of KALINOX® (50% nitrous oxide and oxygen) inhalation has demonstrated analgesic efficacy in various procedures (obstetric, liver biopsy, transrectal ultrasound guided prostate biopsy, emergency) The aim of this study is to investigate the safety and efficacy of analgesia with N2O/O2 inhalation for detrusor BTX-A injections using a rigid cystoscope.
Detailed description
First line treatment for detrusor hyperreflexia is the use of antimuscarinic medications. However, these medications can have unwanted side effects and often are not good enough to decrease incontinence in cases of severe neurogenic detrusor overactivity. Some invasive surgical procedures are possible such as sacral nerve stimulator, sacral rhizotomy, bladder myomectomy and bladder augmentation. But there are still few treatment option for this medical complication. Recently, some data are showed the clinical application of botulinum neurotoxin A (BTX-A) into detrusor muscle in cases of resistant neurogenic detrusor overactivity to conventional treatment with anticholinergic medication. In these studies the authors perform intravesical BTX-A injections. First 300 units Botox are diluted with 30 ml of preservative-free saline. Using a rigid cystoscope and an injection needle, BTX-A is injected into 30 sites within the detrusor muscle.
To reduce the pain, instillation of lidocaine before botulinum-A toxin injections is used into the bladder. On a 10-point rating scale the mean pain score of the patients who underwent the injections of Botox after conventional lidocaine instillation is 4.0 (SD 1.6).
The used of KALINOX® (50% nitrous oxide and oxygen) inhalation has demonstrated analgesic efficacy in various procedures (obstetric, liver biopsy, transrectal ultrasound guided prostate biopsy, emergency…) associated with mild to moderate pain and it is technically simple to use. Early studies indicated that 30% nitrous oxide is equipotent to 10 to 15 mg. morphine. Except in patients with severe chronic obstructive pulmonary disease KALINOX® inhalation is a safe and acceptable method of sedation and analgesia. It is a nonirritant and is excreted unchanged from the lungs.
The aim of this study is to investigate the safety and efficacy of analgesia with N2O/O2 inhalation for detrusor BTX-A injections using a rigid cystoscope. Will be included patient with severe neurogenic detrusor overactivity but with preserved bladder sensibility treated with botulinum-A toxin injections into the detrusor muscle Patients will be randomized into a group that will receive KALINOX® via a breath activated device and a control group that receive oxygen through a similar breathing device. The investigator will be involved in the randomization process since the gas cylinders will be covered and they will be blind to the gas used. All patients involved will be blinded to the gas that they will inhale. The patients will score the injection pain and the anxiety on a 10-point rating scale. Furthermore the duration of the practice will be measured.
The hypothesis is that analgesia with KALINOX® will show a significant difference in pain perception among the 2 groups.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Oxygen | Placebo comparator | Drug: Oxygen |
| Nitrous Oxide | Active comparator | Drug: Nitrous Oxide |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Man or woman of more than 18 years
- Patient with overactive bladder
- First intravesical Botulinum injection
- Bladder sensitivity on the urodynamic
- Patient not presenting contraindication to this injection
Key exclusion criteria (25 listed)
- Pregnancy
- Contraindication in the toxin such as severe myasthenia, syndrome of Eaton-Lambert, or amyotrophic lateral sclerosis
- Treatment antibiotic by aminoglycoside
- Allergies known about the toxin, about the anesthetics used during the study
- Patients under anticoagulants, or having taken a treatment anti-aggregant platelet in 10 days preceding the injection
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 |
|---|---|---|
| Nitrous Oxidenitrous oxide inhalation during intravesical injection. Dose depends on gender and pain | Drug | Nitrous Oxide |
| Oxygenoxygen | Drug | Oxygen |
Primary outcome
Mean pain during intravesical injection
Time frame: 5 minutes
2 secondary outcomes
Maximum pain during intravesical injection
Time frame: 5 minutes
Anxiety during intravesical injection
Time frame: 5 minutes
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 6 Nov 2014.
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.
Pierre DENYS, PUPH principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Nitrous Oxide and Oxygen in people with Injection Site Vesicles, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 8 inclusion and 25 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 6 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Mean pain during intravesical injection (time frame: 5 minutes). 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 6 Nov 2014.