ConstipationPhase 4NCT02977286
Naloxegol to Prevent Lower Gastrointestinal Paralysis in Critically Ill Adults Administered Opioids
A Phase 4 study testing Naloxegol Oral Tablet, Docusate Sodium 100 Mg oral capsule [Colace] and Senna 217 Mg Oral Tablet in people with Constipation, run by Tufts Medical Center at 1 site in United States.
Trial summary
This study evaluates the addition of naloxegol (Movantik) to a laxative protocol in critically ill adults requiring scheduled opioid (e.g. fentanyl) therapy. Half of the participants will receive naloxegol and a laxative protocol and half the participants will receive a placebo and a laxative protocol. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Constipation
- What is being tested?
- Naloxegol Oral Tablet, Docusate Sodium 100 Mg oral capsule [Colace] and Senna 217 Mg Oral Tablet
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jan 2017to 9 Oct 2019
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Age ≥ 18 years
- Admitted to an ICU
- Expected to require admission to an ICU for ≥ 48 hours
- Intravenous opioid administration in the prior 24 hours of ≥ 100 mcg fentanyl equivalents
Who cannot join
- Scheduled use of an opioid ≥ 10 mg morphine equivalents per day in the week prior to ICU admission
- History of constipation (≤ 2 SBM per week and current use of stool softener or laxative therapy) prior to ICU admission
- Current scheduled use of a medication affecting gastric motility
- Current use of a medication known to be a strong CYP3A4 inhibitor
- History of a neurologic condition that may affect the permeability of the blood-brain barrier
- Acute GI condition (e.g., clinical evidence of acute fecal impaction/complete obstruction, acute surgical abdomen, acute GI bleeding)
Show all 17Show fewer
- Condition affecting GI motility or function (e.g. inflammatory bowel disease requiring immunosuppressive therapy, symptomatic Clostridium difficile, active diverticular disease, surgery on the colon or abdomen within 60 days of ICU admission)
- Current use of total parenteral nutrition
- Administration of enteral nutrition through a jejunal tube
- Severe hepatic dysfunction
- Endstage renal disease defined as either i. calculated creatinine clearance ≤ 10ml/min or ii. Any current use of renal replacement therapy
- Inability to enroll in study and initiate study medication within 48 hours of the patient begin first initiated on scheduled IV opioid therapy after ICU admission
- Unreliable method for enteral, gastric and/or oral medication administration (e.g., no feeding tube, nasogastric tube is on suction)
- Current or previous use of an opioid antagonist agent (e.g., naloxegol, methylnaltrexone) in the past 30 days
- Pregnant or actively lactating females
- Current participation in another interventional clinical study
- Inability to obtain informed consent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Impact of Naloxegol on Prevention of Lower GI Tract Paralysis in Critically Ill Adults Initiated on Scheduled Intravenous Opioid Therapy: A Randomized, Double-Blind, Placebo-Controlled, Phase II, Single-Center, Proof of Concept Study
This study evaluates the addition of naloxegol (Movantik) to a laxative protocol in critically ill adults requiring scheduled opioid (e.g. fentanyl) therapy. Half of the participants will receive naloxegol and a laxative protocol and half the participants will receive a placebo and a laxative protocol.
Read the detailed description
Among the more than 5 million adults who are admitted to the ICU each year in the USA, most have pain and thus receive a pain (analgesic) medication called an opioid. Opioid use in critically ill adults continues to increase given the greater awareness of untreated pain in the ICU and that an opioid-first approach be used to optimize patient safety and comfort and improve tolerance with breathing machines (i.e. mechanical ventilation). Similar to constipation, paralysis of the lower gastrointestinal (GI) tract is defined as the inability to pass stool due to impaired gut movement, and is a common effect of opioid use in the critically ill. Lower GI tract paralysis may lead to nausea, vomiting, aspiration, compromise the ability to administer tube feeds (enteral nutrition), an increase abdominal pain, delirium and delay getting off mechanical ventilation. One recent randomized study found that aggressive use of laxatives to prevent lower GI tract paralysis in critically ill adults was associated with lower daily organ dysfunction [as measured by the Sequential Organ Failure Assessment (SOFA) score]. The lower GI tract paralysis that occurs in the critically ill often responds poorly to laxative medication therapy (e.g., senna, bisacodyl, lactulose). While stool softener medications like docusate are routinely administered to patients on opioids, laxative-based protocols are frequently not initiated in the ICU until signs of lower GI tract paralysis start to appear. There is therefore an important and unmet need for a safe and efficacious medication to prevent lower GI tract paralysis in critically ill adults who are initiated on opioid therapy. Naloxegol (Movantik) is a naloxone-like drug that blocks the effect of opioids on the opioid µ receptor in the gut but is not absorbed in the brain (and therefore does not block the pain effects of opioids). Naloxegol is currently approved by the Food and Drug Administration (FDA) for the treatment of opioid-induced constipation (OIC) in non-ICU patients receiving scheduled moderate to high dose opioids for the treatment of chronic non-cancer pain. Naloxegol has a mechanism of action, efficacy, convenience of administration, and safety profile that make it an ideal candidate for use as a preventative medication for lower GI tract paralysis in critically ill adults receiving scheduled opioid therapy. The investigators propose a pilot study in which they will test the hypothesis that naloxegol (versus placebo) will reduce the time to the first spontaneous bowel movement (SBM) that an ICU patient has, that it will prevent lower GI tract paralysis in critically ill adults initiated on scheduled IV opioid therapy, and its use will not result in side effects that are concerning to doctors or patients. The investigators will randomize 36 critically ill ICU patients (18 in each arm) to receive naloxegol [25mg or 12.5mg (in patients with a creatinine clearance ≤ 60ml/min)] or placebo. This pilot study will provide valuable information to help guide future, larger studies evaluating the role of naloxegol in critically ill adults.
- Conditions
- Constipation
- Being tested
- Naloxegol Oral Tablet, Placebo Oral Tablet, Docusate Sodium 100 Mg oral capsule [Colace], Senna 217 Mg Oral Tablet, Polyethylene Glycols
- Medical subject headings
- Constipation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Naloxegol Oral TabletDrug
Also called Movantik
Naloxegol Oral Tablet 25 mg (or 12.5 mg) po (enteral) daily
Placebo Oral TabletDrug
Also called Official AstraZeneca placebo for Movantik
Placebo Oral Tablet po (enteral) twice daily
Docusate Sodium 100 Mg oral capsule [Colace]Drug
Also called Colace
Docusate Sodium 100 mg po (enteral) twice daily
Senna 217 Mg Oral TabletDrug
Also called Senokot
Senna 127 mg oral tablet daily if no spontaneous bowel movement >/=3 days after scheduled opioid initiation; increase to two senna 127 mg tables if no no spontaneous bowel movement >/=4 days after scheduled opioid initiation. Repeat two senna 127 mg tablets if no spontaneous bowel movement >/=5 days after scheduled opioid initiation. Repeat two senna 127 mg tablets if no spontaneous bowel movement >/=6 days after scheduled opioid initiation.
Polyethylene GlycolsDrug
Also called Miralax
Polyethylene Glycols 17 g daily if no spontaneous bowel movement >/=3 days after scheduled opioid initiation; increase to 34 g daily if no spontaneous bowel movement >/=4 days after scheduled opioid initiation. Repeat 34 g daily if no spontaneous bowel movement >/= 5 days after scheduled opioid initiation. Repeat 34 g daily if no spontaneous bowel movement >/= 6 days after scheduled opioid initiation.
Bisacodyl 10 mg SuppositoryDrug
Also called Dulcolax
Insert one suppository if no spontaneous bowel movement >/=4 days after scheduled opioid initiation. Repeat if no spontaneous bowel movement >/= 5 days after scheduled opioid initiation. Repeat if no spontaneous bowel movement >/= 6 days after scheduled opioid initiation.
Magnesium Citrate Oral Liquid ProductDrug
Also called Citromag
Administer one 10 oz bottle if no spontaneous bowel movement >/= 5 days after scheduled opioid initiation.
MethylnaltrexoneDrug
Also called Relistor
Administer 8 mg or 16 mg (depending on subject's weight) subcutaneously x 1 if no spontaneous bowel movement >/= 6 days after scheduled opioid initiation, consult surgery/gastroenterology and discontinue study medication.
| Study group | Role | What they receive |
|---|---|---|
| Naloxegol Oral Tablet | Experimental | Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: Movantik Receives: Drug: Naloxegol Oral Tablet; Drug: Docusate Sodium 100 Mg oral capsule [Colace]; Drug: Senna 217 Mg Oral Tablet; Drug: Polyethylene Glycols; Drug: Bisacodyl 10 mg Suppository; Drug: Magnesium Citrate Oral Liquid Product; Drug: Methylnaltrexone |
| Placebo Oral Tablet | Placebo comparator | Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: AstraZeneca provided Movantik placebo Receives: Drug: Placebo Oral Tablet; Drug: Docusate Sodium 100 Mg oral capsule [Colace]; Drug: Senna 217 Mg Oral Tablet; Drug: Polyethylene Glycols; Drug: Bisacodyl 10 mg Suppository; Drug: Magnesium Citrate Oral Liquid Product; Drug: Methylnaltrexone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to First Spontaneous Bowel Movement (SBM) Administration
Time to first spontaneous bowel movement during ICU admission after randomization
Measured: First occurrence after study randomization during period of ICU admission or a maximum of 10 ICU days
Secondary outcomes (16)
Time to First Spontaneous Bowel Movement (SBM)
Time to first spontaneous bowel movement during the ICU admission after opioid initiation
Measured: First occurrence after initiation of IV opioid therapy during period of ICU admission or a maximum of 10 ICU days
ICU Days Without a SBM
Measured ICU days that subjects did not have a SBM
Measured: During period of ICU admission or a maximum of 10 ICU days
Occurrence of Lower GI Tract Paralysis (≥3 Days Without a SBM)
Measurement is the number of subjects in each group having this occurrence of lower GI tract paralysis during time frame
Measured: From randomization to ICU discharge or a maximum of 10 ICU days
Average Daily Opioid Requirement [in IV Fentanyl Equivalents (mcg Per Day)]
Average daily opioid requirement is converted to IV fentanyl equivalent listed in mcg per day
Measured: From randomization to ICU discharge or a maximum of 10 ICU days
Number of Patients With Loose and Unformed or Liquid SBM
Consistency of SBM is characterized in one of 4 categories: hard and formed, soft but formed, loose and unformed, and liquid. The number listed in the results section is the number of patients who had either loose or liquid SBM (as opposed to hard or soft formed).
Measured: From randomization to ICU discharge or a maximum of 10 ICU days
Number of Patients That Required Use of the Study Laxative Protocol
A 4-step laxative protocol was initiated when there was no spontaneous bowel movement greater than or equal to 3 days time. Data collected on study laxative protocol included any use as well as the highest level needed.
Measured: From randomization to ICU discharge or a maximum of 10 ICU days
Percentage of Daily Goal Reached for Enteral Nutrition Administration
Enteral nutrition is assessed as daily volume in mL and the reported measure is the percentage of daily goal of enteral nutrition met.
Measured: From randomization to ICU discharge or a maximum of 10 ICU days
Daily Fluid Balance
Daily fluid balance measured in mL is the 24 hours ins and outs
Measured: From randomization to ICU discharge or a maximum of 10 ICU days
Daily Maximal Pain Scale Score
Based on the highest daily Visual Analogue Scale-10 or Clinical Pain Observation tool assessment.
VAS-10 is Visual Analogue Scale which uses a nurse-administered 10 point rating scale. A measurement of 0-1 is minimal pain. A measurement of 10 is severe pain.
Measured: From randomization to ICU discharge or a maximum of 10 ICU days
Daily Maximal Sedation Assessment Scale (SAS) Score
The Sedation Assessment Scale is rated 1 to 7. Score of 7 is dangerous agitation. Score of 1 is unarousable. Score of 2 is very sedated. The presence of coma is based on the every 4 hour sedation agitation score scale (SAS) assessment. A score of 1 or 2 any time during the day represents that a coma is present. A score of 3-7 represents a subject with no coma present.
Results listed here is days without coma (SAS score of 3-7)
Measured: From randomization to ICU discharge or a maximum of 10 ICU days
Daily Presence of Delirium Using the Intensive Care Delirium Screening Checklist (ICDSC)
Measures as days without delirium with daily presence of delirium assessed using the Intensive Care Delirium Screening Checklist (ICDSC)
Measured: From randomization to ICU discharge or a maximum of 10 ICU days
Occurrence of Lower GI Tract Paralysis Requiring GI/Surgical Consultation
Number of patients with GI tract paralysis requiring Gastroenterology service or Surgical service consultation
Measured: From randomization to ICU discharge or a maximum of 10 ICU days
Days Without Mechanical Ventilation Support for Duration of ICU Stay
Measure is days without mechanical ventilation for duration of ICU stay as expressed as median and inter-Quartile Range
Measured: From ICU admission to ICU discharge or a maximum of 10 ICU days
Abdominal Pressure Measurement
On days when the patient had a urinary catheter in place for clinical reasons, a bladder pressure transducer was inserted and abdominal pressure was measured. The average daily maximum pressure score for each group is reported.
Measured: From randomization to ICU discharge (or removal of foley catheter) or a maximum of 10 ICU days
Time to First Episode of Diarrhea
The number of patients in each group with > or equal to 1 episode of diarrhea after initiation of study drug. The time to first episode of diarrhea was measured in hours.
Measured: Study drug initiation to first episode of diarrhea in hours.
Daily Difference in the Pre-dose and Post-dose Clinical Opioid Withdrawal Scale (COWS) Score
Patients were evaluated 1 hour before and 2 hours after the administration of each dose of study medication using the Clinical Opioid Withdrawal Scale (COWS). COWS is used to help determine the stage or severity of opiate withdrawal and assess the level of physical dependence on opioids. The COWS score ranges from 0-36+. A score of 0 is no active opioid withdrawal. A score of 5-12 is mild; 13-24 is moderate; 25-36 is moderately severe and more than 36 is severe opioid withdrawal.
Measured: One hour before the daily study drug administration and 2 hours after the daily study drug administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2016 (estimated)
- Study start1 Jan 2017
- Primary completion9 Oct 2019
- Study completion9 Oct 2019
Why it stopped: Poor enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for ConstipationStudies 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tufts Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Erik Garpestad, MD, Principal investigator, Tufts Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02977286
- Sponsor's protocol ID
- 11200
- Status last verified
- Feb 2023
- First submitted
- 21 Nov 2016
- Last updated
- 16 Feb 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Reintam Blaser A, Malbrain ML, Starkopf J, Fruhwald S, Jakob SM, De Waele J, Braun JP, Poeze M, Spies C. Gastrointestinal function in intensive care patients: terminology, definitions and management. Recommendations of the ESICM Working Group on Abdominal Problems. Intensive Care Med. 2012 Mar;38(3):384-94. doi: 10.1007/s00134-011-2459-y. Epub 2012 Feb 7.
PubMed 22310869de Azevedo RP, Freitas FG, Ferreira EM, Pontes de Azevedo LC, Machado FR. Daily laxative therapy reduces organ dysfunction in mechanically ventilated patients: a phase II randomized controlled trial. Crit Care. 2015 Sep 16;19(1):329. doi: 10.1186/s13054-015-1047-x.
PubMed 26373705
Study at a glance
From the registry record, last updated by the sponsor on 16 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Naloxegol on Prevention of Lower GI Tract Paralysis in Critically Ill Adults Initiated on Scheduled Intravenous Opioid Therapy: A Randomized, Double-Blind, Placebo-Controlled, Phase II, Single-Center, Proof of Concept Study
- ClinicalTrials.gov ID
- NCT02977286
- Acronym / sponsor ID
- 11200
- Conditions
- Constipation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poor enrollment
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Tufts Medical CenterUniversity, hospital or other
- Study start
- 1 Jan 2017 (actual)
- Primary completion
- 9 Oct 2019 (actual)
- Study completion
- 9 Oct 2019 (actual)
- First posted
- 30 Nov 2016 (estimated)
- Results
- Posted 16 Feb 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates the addition of naloxegol (Movantik) to a laxative protocol in critically ill adults requiring scheduled opioid (e.g. fentanyl) therapy. Half of the participants will receive naloxegol and a laxative protocol and half the participants will receive a placebo and a laxative protocol.
Detailed description
Among the more than 5 million adults who are admitted to the ICU each year in the USA, most have pain and thus receive a pain (analgesic) medication called an opioid. Opioid use in critically ill adults continues to increase given the greater awareness of untreated pain in the ICU and that an opioid-first approach be used to optimize patient safety and comfort and improve tolerance with breathing machines (i.e. mechanical ventilation). Similar to constipation, paralysis of the lower gastrointestinal (GI) tract is defined as the inability to pass stool due to impaired gut movement, and is a common effect of opioid use in the critically ill. Lower GI tract paralysis may lead to nausea, vomiting, aspiration, compromise the ability to administer tube feeds (enteral nutrition), an increase abdominal pain, delirium and delay getting off mechanical ventilation. One recent randomized study found that aggressive use of laxatives to prevent lower GI tract paralysis in critically ill adults was associated with lower daily organ dysfunction [as measured by the Sequential Organ Failure Assessment (SOFA) score]. The lower GI tract paralysis that occurs in the critically ill often responds poorly to laxative medication therapy (e.g., senna, bisacodyl, lactulose). While stool softener medications like docusate are routinely administered to patients on opioids, laxative-based protocols are frequently not initiated in the ICU until signs of lower GI tract paralysis start to appear. There is therefore an important and unmet need for a safe and efficacious medication to prevent lower GI tract paralysis in critically ill adults who are initiated on opioid therapy. Naloxegol (Movantik) is a naloxone-like drug that blocks the effect of opioids on the opioid µ receptor in the gut but is not absorbed in the brain (and therefore does not block the pain effects of opioids). Naloxegol is currently approved by the Food and Drug Administration (FDA) for the treatment of opioid-induced constipation (OIC) in non-ICU patients receiving scheduled moderate to high dose opioids for the treatment of chronic non-cancer pain. Naloxegol has a mechanism of action, efficacy, convenience of administration, and safety profile that make it an ideal candidate for use as a preventative medication for lower GI tract paralysis in critically ill adults receiving scheduled opioid therapy. The investigators propose a pilot study in which they will test the hypothesis that naloxegol (versus placebo) will reduce the time to the first spontaneous bowel movement (SBM) that an ICU patient has, that it will prevent lower GI tract paralysis in critically ill adults initiated on scheduled IV opioid therapy, and its use will not result in side effects that are concerning to doctors or patients. The investigators will randomize 36 critically ill ICU patients (18 in each arm) to receive naloxegol [25mg or 12.5mg (in patients with a creatinine clearance ≤ 60ml/min)] or placebo. This pilot study will provide valuable information to help guide future, larger studies evaluating the role of naloxegol in critically ill adults.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Naloxegol Oral Tablet | Experimental | Drug: Naloxegol Oral Tablet, Drug: Docusate Sodium 100 Mg oral capsule [Colace], Drug: Senna 217 Mg Oral Tablet, Drug: Polyethylene Glycols, Drug: Bisacodyl 10 mg Suppository, Drug: Magnesium Citrate Oral Liquid Product, Drug: MethylnaltrexoneIntervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following: 1. Adverse event potentially attributable to the study drug. 2. Use of Relistor. 3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment. 4. The participant has been administered 10 days of study medication. 5. The participant is discharged from the ICU. 6. The participant requires the initiation of a strong CYP3A4 inhibitor medication. Other Name: Movantik |
| Placebo Oral Tablet | Placebo comparator | Drug: Placebo Oral Tablet, Drug: Docusate Sodium 100 Mg oral capsule [Colace], Drug: Senna 217 Mg Oral Tablet, Drug: Polyethylene Glycols, Drug: Bisacodyl 10 mg Suppository, Drug: Magnesium Citrate Oral Liquid Product, Drug: MethylnaltrexoneIntervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following: 1. Adverse event potentially attributable to the study drug. 2. Use of Relistor. 3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment. 4. The participant has been administered 10 days of study medication. 5. The participant is discharged from the ICU. 6. The participant requires the initiation of a strong CYP3A4 inhibitor medication. Other Name: AstraZeneca provided Movantik placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age ≥ 18 years
- Admitted to an ICU
- Expected to require admission to an ICU for ≥ 48 hours
- Intravenous opioid administration in the prior 24 hours of ≥ 100 mcg fentanyl equivalents
Key exclusion criteria (17 listed)
- Scheduled use of an opioid ≥ 10 mg morphine equivalents per day in the week prior to ICU admission
- History of constipation (≤ 2 SBM per week and current use of stool softener or laxative therapy) prior to ICU admission
- Current scheduled use of a medication affecting gastric motility
- Current use of a medication known to be a strong CYP3A4 inhibitor
- History of a neurologic condition that may affect the permeability of the blood-brain barrier
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 |
|---|---|---|
| Naloxegol Oral TabletAlso: MovantikNaloxegol Oral Tablet 25 mg (or 12.5 mg) po (enteral) daily | Drug | Naloxegol Oral Tablet |
| Placebo Oral TabletAlso: Official AstraZeneca placebo for MovantikPlacebo Oral Tablet po (enteral) twice daily | Drug | Placebo Oral Tablet |
| Docusate Sodium 100 Mg oral capsule [Colace]Also: ColaceDocusate Sodium 100 mg po (enteral) twice daily | Drug | Naloxegol Oral Tablet, Placebo Oral Tablet |
| Senna 217 Mg Oral TabletAlso: SenokotSenna 127 mg oral tablet daily if no spontaneous bowel movement >/=3 days after scheduled opioid initiation; increase to two senna 127 mg tables if no no spontaneous bowel movement >/=4 days after scheduled opioid initiation. Repeat two senna 127 mg tablets if no spontaneous bowel movement >/=5 days after scheduled opioid initiation. Repeat two senna 127 mg tablets if no spontaneous bowel movement >/=6 days after scheduled opioid initiation. | Drug | Naloxegol Oral Tablet, Placebo Oral Tablet |
| Polyethylene GlycolsAlso: MiralaxPolyethylene Glycols 17 g daily if no spontaneous bowel movement >/=3 days after scheduled opioid initiation; increase to 34 g daily if no spontaneous bowel movement >/=4 days after scheduled opioid initiation. Repeat 34 g daily if no spontaneous bowel movement >/= 5 days after scheduled opioid initiation. Repeat 34 g daily if no spontaneous bowel movement >/= 6 days after scheduled opioid initiation. | Drug | Naloxegol Oral Tablet, Placebo Oral Tablet |
| Bisacodyl 10 mg SuppositoryAlso: DulcolaxInsert one suppository if no spontaneous bowel movement >/=4 days after scheduled opioid initiation. Repeat if no spontaneous bowel movement >/= 5 days after scheduled opioid initiation. Repeat if no spontaneous bowel movement >/= 6 days after scheduled opioid initiation. | Drug | Naloxegol Oral Tablet, Placebo Oral Tablet |
| Magnesium Citrate Oral Liquid ProductAlso: CitromagAdminister one 10 oz bottle if no spontaneous bowel movement >/= 5 days after scheduled opioid initiation. | Drug | Naloxegol Oral Tablet, Placebo Oral Tablet |
| MethylnaltrexoneAlso: RelistorAdminister 8 mg or 16 mg (depending on subject's weight) subcutaneously x 1 if no spontaneous bowel movement >/= 6 days after scheduled opioid initiation, consult surgery/gastroenterology and discontinue study medication. | Drug | Naloxegol Oral Tablet, Placebo Oral Tablet |
Primary outcome
Time to First Spontaneous Bowel Movement (SBM) Administration
Time frame: First occurrence after study randomization during period of ICU admission or a maximum of 10 ICU days
Time to first spontaneous bowel movement during ICU admission after randomization
16 secondary outcomes
Time to First Spontaneous Bowel Movement (SBM)
Time frame: First occurrence after initiation of IV opioid therapy during period of ICU admission or a maximum of 10 ICU days
ICU Days Without a SBM
Time frame: During period of ICU admission or a maximum of 10 ICU days
Occurrence of Lower GI Tract Paralysis (≥3 Days Without a SBM)
Time frame: From randomization to ICU discharge or a maximum of 10 ICU days
Average Daily Opioid Requirement [in IV Fentanyl Equivalents (mcg Per Day)]
Time frame: From randomization to ICU discharge or a maximum of 10 ICU days
Number of Patients With Loose and Unformed or Liquid SBM
Time frame: From randomization to ICU discharge or a maximum of 10 ICU days
Number of Patients That Required Use of the Study Laxative Protocol
Time frame: From randomization to ICU discharge or a maximum of 10 ICU days
Percentage of Daily Goal Reached for Enteral Nutrition Administration
Time frame: From randomization to ICU discharge or a maximum of 10 ICU days
Daily Fluid Balance
Time frame: From randomization to ICU discharge or a maximum of 10 ICU days
Daily Maximal Pain Scale Score
Time frame: From randomization to ICU discharge or a maximum of 10 ICU days
Daily Maximal Sedation Assessment Scale (SAS) Score
Time frame: From randomization to ICU discharge or a maximum of 10 ICU days
Daily Presence of Delirium Using the Intensive Care Delirium Screening Checklist (ICDSC)
Time frame: From randomization to ICU discharge or a maximum of 10 ICU days
Occurrence of Lower GI Tract Paralysis Requiring GI/Surgical Consultation
Time frame: From randomization to ICU discharge or a maximum of 10 ICU days
Days Without Mechanical Ventilation Support for Duration of ICU Stay
Time frame: From ICU admission to ICU discharge or a maximum of 10 ICU days
Abdominal Pressure Measurement
Time frame: From randomization to ICU discharge (or removal of foley catheter) or a maximum of 10 ICU days
Time to First Episode of Diarrhea
Time frame: Study drug initiation to first episode of diarrhea in hours.
Daily Difference in the Pre-dose and Post-dose Clinical Opioid Withdrawal Scale (COWS) Score
Time frame: One hour before the daily study drug administration and 2 hours after the daily study drug administration
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Feb 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22310869Reintam Blaser A, Malbrain ML, Starkopf J, Fruhwald S, Jakob SM, De Waele J, Braun JP, Poeze M, Spies C. Gastrointestinal function in intensive care patients: terminology, definitions and management. Recommendations of the ESICM Working Group on Abdominal Problems. Intensive Care Med. 2012 Mar;38(3):384-94. doi: 10.1007/s00134-011-2459-y. Epub 2012 Feb 7.
- Background: PubMed 26373705de Azevedo RP, Freitas FG, Ferreira EM, Pontes de Azevedo LC, Machado FR. Daily laxative therapy reduces organ dysfunction in mechanically ventilated patients: a phase II randomized controlled trial. Crit Care. 2015 Sep 16;19(1):329. doi: 10.1186/s13054-015-1047-x.
- Individual participant dataSharing planned: No
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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.
Erik Garpestad, MD principal investigator
Tufts Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Naloxegol Oral Tablet, Docusate Sodium 100 Mg oral capsule [Colace] and Senna 217 Mg Oral Tablet in people with Constipation, run by Tufts Medical Center at 1 site in United States.
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 4 inclusion and 17 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: stopped early, as of the sponsor's last update on 16 Feb 2023. 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 United States. 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?
Yes. Results are posted in the registry (first posted 16 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Time to First Spontaneous Bowel Movement (SBM) Administration (time frame: First occurrence after study randomization during period of ICU admission or a maximum of 10 ICU days). 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 NCT02977286, which also lists 2 linked publications.
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 16 Feb 2023.