STEMIPhase 4MOVEMENTNCT02942550
Methylnaltrexone as a Method to Improve Ticagrelor Uptake in Morphine Treated STEMI Patients
A Phase 4 study testing Methylnaltrexone bromide (Relistor®). and Sodium Chloride 9mg/mL in people with STEMI and Morphine, run by Karolinska University Hospital at 2 sites in Sweden.
Trial summary
This study will examine the impact of the peripheral opioid antagonist methylnaltrexone on the onset of effect of ticagrelor in morphine treated patients with ST elevation myocardial infarction (STEMI). Half of the participants will receive methylnaltrexone, while the other half will receive placebo. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- STEMI, Morphine, Ticagrelor
- What is being tested?
- Methylnaltrexone bromide (Relistor®). and Sodium Chloride 9mg/mL
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 82 participants
- Where
- 2 sitesSweden
- Study dates
- Nov 2016to Dec 2017
- Phase
- Phase 4
- 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
- Diagnosis of STEMI
- Administration of a 180 mg loading dose ticagrelor
- Analgesic treatment with intravenous morphine pre-PCI
Who cannot join
- Cardiac arrest
- Body weight > 114kg
- Vomiting after intake of ticagrelor loading dose
- Use of Naloxone before inclusion or during sampling period
- Inability to understand study outline and instructions
- Methylnaltrexone bromide contraindication
Show all 10Show fewer
- Age <18 years; 8) Women in fertile age
- Administration of ticagrelor during the week before inclusion
- Treatment with Cangrexal
- Ongoing long-term opioid treatment.
Trial locations and contacts
2 sites in 1 country.
Sweden2 sites
Karolinska University Hospital
Stockholm
Södersjukhuset (Stockholm South General Hospital)
Stockholm
About this study
Official title: Methylnaltrexone as a Method to imprOVE Platelet Inhibition of Ticagrelor in Morphine-treated Patients With ST-segMENT Elevation Myocardial Infarction: a Prospective, Single Blinded Randomized, Placebo-controlled Trial
This study will examine the impact of the peripheral opioid antagonist methylnaltrexone on the onset of effect of ticagrelor in morphine treated patients with ST elevation myocardial infarction (STEMI). Half of the participants will receive methylnaltrexone, while the other half will receive placebo.
Read the detailed description
The rate of drug absorption in the gastro-intestinal tract is often determined by the rate of gastric emptying. Morphine treatment, which is frequently given in order to relieve pain in patients with STEMI, is known to delay gastric emptying, and has indeed emerged as a predictor of delayed/poor antiplatelet response in patients receiving oral prasugrel or ticagrelor.
In recent years, morphine has been found to delay the onset of oral P2Y12-inhibitors. To counteract this, the investigators hypothesized that an opioid antagonist may be used. The opioid antagonist naloxone has previously been shown to reduce the morphine induced delay in gastric emptying However, naloxone crosses the blood-brain barrier (BBB) and reduces the pain relieving effects of morphine. In contrast, the morphine antagonist methylnaltrexone has a reduced passage over the BBB and acts primarily as a peripheral morphine antagonist without affecting the morphine-mediated central analgesic effects.
The aim of the planned study is to evaluate whether methylnaltrexone bromide may reduce the morphine induced delay in onset of platelet inhibition after a loading dose of 180 mg ticagrelor in morphine treated patients with STEMI undergoing primary percutaneous coronary intervention (PCI), where a rapid and adequate platelet inhibition after the administration of ticagrelor is crucial. As morphine is an inclusion criterion, all patients included in the study will be on morphine treatment. Thus, morphine treatment is not an intervention to be administered as part of the protocol. Stratification according to inferior and anterior/lateral STEMI will be perform to avoid imbalance in the location of myocardial infarction between the groups.
- Conditions
- STEMI, Morphine, Ticagrelor, Methylnaltrexone
- Being tested
- Methylnaltrexone bromide (Relistor®)., Sodium Chloride 9mg/mL
- Medical subject headings
- ST Elevation Myocardial Infarction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Methylnaltrexone bromide (Relistor®).Drug
Sodium Chloride 9mg/mLDrug
| Study group | Role | What they receive |
|---|---|---|
| Methylnaltrexone | Active comparator | Methylnaltrexone bromide (Relistor®). Single intravenous injection of 8 mg (0.4 ml solution) for patients weighing 38-61 kg or 12 mg (0.6 ml solution) patients weighing 62-114 kg). Receives: Drug: Methylnaltrexone bromide (Relistor®). |
| Placebo | Placebo comparator | Sodium Chloride, 9mg /mL ingle intravenous injection of 0.4 mL solution for patients weighing 38-61 kg or 0.6 mL solution patients weighing 62-114 kg). Receives: Drug: Sodium Chloride 9mg/mL |
What is being measured
The primary outcome is the main question the study is designed to answer.
High on-treatment platelet reactivity (HPR)
HPR defined as platelet reactivity index (PRI) ≥50% using VASP analysis
Measured: Two hours after the injection of either active drug or placebo
Number of participants with serious adverse events
Serious AE is any untoward medical occurrence that at any dose:
- Results in death.
- Is life-threatening at the time of the event.
- Requires inpatient hospitalization.
- Requires prolongation of existing hospitalization.
- Results in persistent or significant disability/incapacity.
- Is a congenital anomaly/birth defect.
Measured: Within 48 hours after drug administration
Secondary outcomes (5)
High on-treatment platelet reactivity
Measured: One hour after the injection of either active drug or placebo
Difference in ticagrelor and AR-C124910XX concentrations
Measured: One and two hours after the injection of either active drug or placebo
Change in patient pain according to visual analog scale
Measured: One and two hours after the injection of either active drug or placebo
Difference in ticagrelor and AR-C124910XX concentrations between patients with inferior STEMI and patients with anterior/lateral STEMI.
Measured: One and two hours after the injection of either active drug or placebo
Difference in high on-treatment platelet reactivity (HPR) between patients with inferior STEMI and patients with anterior/lateral STEMI.
HPR defined as platelet reactivity index (PRI) ≥50% using VASP analysis
Measured: One and two hours after the injection of either active drug or placebo
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2016 (estimated)
- Study startNov 2016
- Primary completionDec 2017
- Study completionDec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for STEMIStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 82 participants (actual)
Sponsor and investigators
- Lead sponsor
- Karolinska University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jan van der Linden, Karolinska University Hospital
- Investigators
- Per Tornvall, MD, PhD, Principal investigator, Karolinska InstitutetUlf Jensen, MD, PhD, Principal investigator, Karolinska InstitutetNawzad Saleh, MD, PhD, Principal investigator, Karolinska InstitutetLoghman Henareh, MD; PhD, Principal investigator, Karolinska Institutet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02942550
- Sponsor's protocol ID
- 880526
- Acronym
- MOVEMENT
- Status last verified
- Apr 2018
- First submitted
- 21 Sep 2016
- Last updated
- 9 Apr 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No: Data will only be published on a group level.
Publications
Holm M, Tornvall P, Henareh L, Jensen U, Golster N, Alstrom P, Santos-Pardo I, Witt N, Fedchenko N, Venetsanos D, Beck O, van der Linden J. The MOVEMENT Trial. J Am Heart Assoc. 2019 Jan 22;8(2):e010152. doi: 10.1161/JAHA.118.010152.
PubMed 30636504
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Methylnaltrexone as a Method to imprOVE Platelet Inhibition of Ticagrelor in Morphine-treated Patients With ST-segMENT Elevation Myocardial Infarction: a Prospective, Single Blinded Randomized, Placebo-controlled Trial
- ClinicalTrials.gov ID
- NCT02942550
- Acronym / sponsor ID
- MOVEMENT / 880526
- Conditions
- STEMI, Morphine, Ticagrelor, Methylnaltrexone
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 82 participants (actual)
- Lead sponsor
- Karolinska University HospitalUniversity, hospital or other
- Study start
- Nov 2016 (actual)
- Primary completion
- Dec 2017 (actual)
- Study completion
- Dec 2017 (actual)
- First posted
- 24 Oct 2016 (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.
This study will examine the impact of the peripheral opioid antagonist methylnaltrexone on the onset of effect of ticagrelor in morphine treated patients with ST elevation myocardial infarction (STEMI). Half of the participants will receive methylnaltrexone, while the other half will receive placebo.
Detailed description
The rate of drug absorption in the gastro-intestinal tract is often determined by the rate of gastric emptying. Morphine treatment, which is frequently given in order to relieve pain in patients with STEMI, is known to delay gastric emptying, and has indeed emerged as a predictor of delayed/poor antiplatelet response in patients receiving oral prasugrel or ticagrelor.
In recent years, morphine has been found to delay the onset of oral P2Y12-inhibitors. To counteract this, the investigators hypothesized that an opioid antagonist may be used. The opioid antagonist naloxone has previously been shown to reduce the morphine induced delay in gastric emptying However, naloxone crosses the blood-brain barrier (BBB) and reduces the pain relieving effects of morphine. In contrast, the morphine antagonist methylnaltrexone has a reduced passage over the BBB and acts primarily as a peripheral morphine antagonist without affecting the morphine-mediated central analgesic effects.
The aim of the planned study is to evaluate whether methylnaltrexone bromide may reduce the morphine induced delay in onset of platelet inhibition after a loading dose of 180 mg ticagrelor in morphine treated patients with STEMI undergoing primary percutaneous coronary intervention (PCI), where a rapid and adequate platelet inhibition after the administration of ticagrelor is crucial. As morphine is an inclusion criterion, all patients included in the study will be on morphine treatment. Thus, morphine treatment is not an intervention to be administered as part of the protocol. Stratification according to inferior and anterior/lateral STEMI will be perform to avoid imbalance in the location of myocardial infarction between the groups.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Methylnaltrexone | Active comparator | Drug: Methylnaltrexone bromide (Relistor®).Methylnaltrexone bromide (Relistor®). Single intravenous injection of 8 mg (0.4 ml solution) for patients weighing 38-61 kg or 12 mg (0.6 ml solution) patients weighing 62-114 kg). |
| Placebo | Placebo comparator | Drug: Sodium Chloride 9mg/mLSodium Chloride, 9mg /mL ingle intravenous injection of 0.4 mL solution for patients weighing 38-61 kg or 0.6 mL solution patients weighing 62-114 kg). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Diagnosis of STEMI
- Administration of a 180 mg loading dose ticagrelor
- Analgesic treatment with intravenous morphine pre-PCI
Key exclusion criteria (10 listed)
- Cardiac arrest
- Body weight > 114kg
- Vomiting after intake of ticagrelor loading dose
- Use of Naloxone before inclusion or during sampling period
- Inability to understand study outline and instructions
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 |
|---|---|---|
| Methylnaltrexone bromide (Relistor®). | Drug | Methylnaltrexone |
| Sodium Chloride 9mg/mL | Drug | Placebo |
Primary outcome
High on-treatment platelet reactivity (HPR)
Time frame: Two hours after the injection of either active drug or placebo
HPR defined as platelet reactivity index (PRI) ≥50% using VASP analysis
Number of participants with serious adverse events
Time frame: Within 48 hours after drug administration
Serious AE is any untoward medical occurrence that at any dose: * Results in death. * Is life-threatening at the time of the event. * Requires inpatient hospitalization. * Requires prolongation of existing hospitalization. * Results in persistent or significant disability/incapacity. * Is a congenital anomaly/birth defect.
5 secondary outcomes
High on-treatment platelet reactivity
Time frame: One hour after the injection of either active drug or placebo
Difference in ticagrelor and AR-C124910XX concentrations
Time frame: One and two hours after the injection of either active drug or placebo
Change in patient pain according to visual analog scale
Time frame: One and two hours after the injection of either active drug or placebo
Difference in ticagrelor and AR-C124910XX concentrations between patients with inferior STEMI and patients with anterior/lateral STEMI.
Time frame: One and two hours after the injection of either active drug or placebo
Difference in high on-treatment platelet reactivity (HPR) between patients with inferior STEMI and patients with anterior/lateral STEMI.
Time frame: One and two hours after the injection of either active drug or placebo
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 9 Apr 2018.
- Derived from this study: PubMed 30636504Holm M, Tornvall P, Henareh L, Jensen U, Golster N, Alstrom P, Santos-Pardo I, Witt N, Fedchenko N, Venetsanos D, Beck O, van der Linden J. The MOVEMENT Trial. J Am Heart Assoc. 2019 Jan 22;8(2):e010152. doi: 10.1161/JAHA.118.010152.
- Individual participant dataSharing planned: No. Data will only be published on a group level.
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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.
Per Tornvall, MD, PhD principal investigator
Karolinska Institutet
Ulf Jensen, MD, PhD principal investigator
Karolinska Institutet
Nawzad Saleh, MD, PhD principal investigator
Karolinska Institutet
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Methylnaltrexone bromide (Relistor®). and Sodium Chloride 9mg/mL in people with STEMI and Morphine, run by Karolinska University Hospital at 2 sites in Sweden.
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 3 inclusion and 10 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 9 Apr 2018. 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 Sweden. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
High on-treatment platelet reactivity (HPR) (time frame: Two hours after the injection of either active drug or placebo). 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?
On the ClinicalTrials.gov record for NCT02942550, which also lists 1 linked publication.
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 9 Apr 2018.