Ogilvie SyndromePhase 4NCT04951726
Neostigmine Route for Acute Colonic Pseudo Obstruction
A Phase 4 study testing Neostigmine in people with Ogilvie Syndrome, run by University of Southern California at 1 site in United States.
Trial summary
Neostigmine is commonly used for medical treatment of acute colonic pseudo obstruction, however, the ideal route of administration has not been determined. Though IV push works rapidly, it is likely associated with the most side effects. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Ogilvie Syndrome
- What is being tested?
- Neostigmine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Feb 2022to 1 Aug 2025
- 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 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients with radiologically confirmed acute colonic pseudo obstruction (ACPO).
- Plain abdominal radiograph or computed tomography imaging
- Cecal diameter of >9 cm or transverse colon diameter of >6 cm
- Distal obstruction ruled out on imaging (Contrast enema, endoscopy, CT scan)
Who cannot join
- Patients with previous neostigmine administration during current hospitalization
- Patients with prior attempt at endoscopic decompression on this admission.
- Patients with base-line heart rate of less than 60 beats per minute or on beta blocker medication
- Patients with systolic blood pressure of less than 90 mm Hg
- Signs of bowel perforation, with peritoneal signs on physical examination or free air on radiographs
- Active bronchospasm requiring medication
Show all 12Show fewer
- Treatment with prokinetic drugs such as cisapride or metoclopramide in the 24 hours before evaluation
- A history of colon cancer or partial colonic resection
- Signs concerning for colonic obstruction
- Active gastrointestinal bleeding
- Pregnancy
- Serum creatinine concentration of more than 3 mg per deciliter (265μmol per liter).
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
Los Angeles University of Southern California Medical Center
Los Angeles, California, 90004
Meghan Lewis, 310-801-4070, meghan.lewis@med.usc.edu
About this study
Official title: Evaluating the Safety and Efficacy of Different Routes of Neostigmine Administration for Acute Colonic Pseudo Obstruction: a Prospective Randomized Trial
Neostigmine is commonly used for medical treatment of acute colonic pseudo obstruction, however, the ideal route of administration has not been determined. Though IV push works rapidly, it is likely associated with the most side effects. This study will compare the efficacy and side effect profile of 2 potential routes of administration: IV push and subcutaneous.
Read the detailed description
Acute colonic pseudo-obstruction (ACPO) is a severe form of colonic ileus seen in patients hospitalized with a variety of medical and surgical conditions. The most serious complication is spontaneous colonic perforation, which occurs in 3% of cases with a mortality rate of up to 50%. The risk of perforation is greater in those patients with a cecal diameter >12 cm, although the duration of dilation might be more important than the cecal diameter. A significant number of patients will respond to the conservative measures enumerated in the abstract.
Endoscopic decompression of the dilated colon is undertaken commonly to prevent spontaneous perforation. However, it is performed under suboptimal conditions (unprepared and distended colon) increasing the risk of complications with a morbidity rate of 3% and a mortality rate of 1%. Furthermore, although effective initially in 69% of cases, 40% of them will have at least one recurrence. To decrease this recurrence rate, endoscopic placement of a drainage tube is now advocated. Patients who fail to respond to conservative therapy and colonoscopic decompression will require surgery, which has a mortality rate of up to 26%.
In an effort to find a more effective, noninvasive therapy, Ponec et al., introduced and highlighted the effect of IV neostigmine (2 mg over 3-5 min). Neostigmine was significantly more effective than placebo in rapidly decreasing colonic dilation in the majority of patients with ACPO. Although it has a short half-life, a single IV dose of 2 mg of neostigmine was sufficient in most cases to restore colonic motility.
It is important to be aware of contraindications to using parasympathetic agents, including bradyarrhythmia and history of bronchospasm. Patients need to be monitored while neostigmine is infused, and atropine should be available in the event of complications. Patients with renal insufficiency might be at higher risk of complications as a significant quantity of the drug is excreted in urine.
In light of these contraindications, administration by the subcutaneous (SQ) route has been utilized intermittently for ACPO. Data for use of SQ administration of neostigmine in adult patients are limited to one multi-institutional observational study, one case series, and two case reports in acute medical and palliative care patients. Although these case reports describe a range of dosing, the SQ route of administration appears to be attractive alternative to IV administration for this indication, with a time to effect of 8 to 10 hours.
This study is a prospective randomized non-inferiority trial that seeks to analyze the success of two different routes of neostigmine administration, sub-cutaneous and IV push, for safety and efficacy in the ACPO patient population.
- Conditions
- Ogilvie Syndrome
- Being tested
- Neostigmine
- Medical subject headings
- Colonic Pseudo-Obstruction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NeostigmineDrug
Also called Bloxierz, Vagostigmin, Prostigmin
cholinesterase inhibitor
| Study group | Role | What they receive |
|---|---|---|
| IV push | Active comparator | 2 mg slow intravenous injection over five minutes repeated q12hr until resolution for up to 24 hours. (4 mg total in 24 hours) Receives: Drug: Neostigmine |
| subcutaneous | Experimental | 1.0 mg subcutaneous repeated q8hr until resolution for up to 24 hours (3.0 mg total in 24 hours) Receives: Drug: Neostigmine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with radiographic resolution of colonic pseudo obstruction
Number of patients who have cecal diameter <9 cm AND transverse diameter <6 cm on abdominal x-ray within 24h of initiation of neostigmine therapy.
Measured: 24 hours
Secondary outcomes (2)
Number of patients with recurrence of colonic pseudo obstruction
Number of patients with recurrence of cecal diameter >9cm or transverse colon diameter >6cm
Measured: 7 days
Number of patients with adverse medication reactions
Number of patients that experience cardiac arrest; bradycardia, defined as a heart rate less than 60 beats/min; sustained hypotension, defined as a mean arterial pressure (MAP) less than 60 >2 min, bronchospasm documented in the medical record and needing emergent administration of albuterol or ipratropium-albuterol within 30 minutes of the dose; nausea documented in the medical record and need for emergent administration of an antiemetic within 30 minutes of the dose; or severe salivation, lacrimation, or diarrhea leading to drug discontinuation
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2021
- Study start4 Feb 2022
- Primary completion1 Aug 2025 (estimated)
- Study completion1 Aug 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Ogilvie SyndromeStudies of the same condition, open and under way.
- More trials run by University of Southern CaliforniaThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Prospective randomized non-inferiority trial 2 Arms: 1. 1.0 mg subcutaneous repeated q8hr until resolution for up to 24 hours (3.0 mg total in 24 hours) 2. 2 mg slow intravenous injection over five minutes repeated q6hr until resolution for up to 24 hours. (8 mg total in 24 hours) (CONTROL GROUP)
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Southern California
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Meghan Lewis, University of Southern California
- Investigators
- Meghan Lewis, MD, Principal investigator, University of Southern California
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04951726
- Sponsor's protocol ID
- 20-07318
- Status last verified
- Aug 2023
- First submitted
- 5 May 2021
- Last updated
- 25 Aug 2023
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
DeMets DL, Lan KK. Interim analysis: the alpha spending function approach. Stat Med. 1994 Jul 15-30;13(13-14):1341-52; discussion 1353-6. doi: 10.1002/sim.4780131308.
PubMed 7973215Frankel A, Gillespie C, Lu CT, Hewett P, Wattchow D. Subcutaneous neostigmine appears safe and effective for acute colonic pseudo-obstruction (Ogilvie's syndrome). ANZ J Surg. 2019 Jun;89(6):700-705. doi: 10.1111/ans.15265. Epub 2019 May 13.
PubMed 31083785Ponec RJ, Saunders MD, Kimmey MB. Neostigmine for the treatment of acute colonic pseudo-obstruction. N Engl J Med. 1999 Jul 15;341(3):137-41. doi: 10.1056/NEJM199907153410301.
PubMed 10403850Kram B, Greenland M, Grant M, Campbell ME, Wells C, Sommer C. Efficacy and Safety of Subcutaneous Neostigmine for Ileus, Acute Colonic Pseudo-obstruction, or Refractory Constipation. Ann Pharmacother. 2018 Jun;52(6):505-512. doi: 10.1177/1060028018754302. Epub 2018 Jan 23.
PubMed 29359574Ilban O, Cicekci F, Celik JB, Bas MA, Duman A. Neostigmine treatment protocols applied in acute colonic pseudo-obstruction disease: A retrospective comparative study. Turk J Gastroenterol. 2019 Mar;30(3):228-233. doi: 10.5152/tjg.2018.18193.
PubMed 30541715van der Spoel JI, Oudemans-van Straaten HM, Stoutenbeek CP, Bosman RJ, Zandstra DF. Neostigmine resolves critical illness-related colonic ileus in intensive care patients with multiple organ failure--a prospective, double-blind, placebo-controlled trial. Intensive Care Med. 2001 May;27(5):822-7. doi: 10.1007/s001340100926.
PubMed 11430537Sgouros SN, Vlachogiannakos J, Vassiliadis K, Bergele C, Stefanidis G, Nastos H, Avgerinos A, Mantides A. Effect of polyethylene glycol electrolyte balanced solution on patients with acute colonic pseudo obstruction after resolution of colonic dilation: a prospective, randomised, placebo controlled trial. Gut. 2006 May;55(5):638-42. doi: 10.1136/gut.2005.082099. Epub 2005 Nov 23.
PubMed 16306137Vogel JD, Feingold DL, Stewart DB, Turner JS, Boutros M, Chun J, Steele SR. Clinical Practice Guidelines for Colon Volvulus and Acute Colonic Pseudo-Obstruction. Dis Colon Rectum. 2016 Jul;59(7):589-600. doi: 10.1097/DCR.0000000000000602. No abstract available.
PubMed 27270510
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating the Safety and Efficacy of Different Routes of Neostigmine Administration for Acute Colonic Pseudo Obstruction: a Prospective Randomized Trial
- ClinicalTrials.gov ID
- NCT04951726
- Acronym / sponsor ID
- 20-07318
- Conditions
- Ogilvie Syndrome
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- University of Southern CaliforniaUniversity, hospital or other
- Study start
- 4 Feb 2022 (actual)
- Primary completion
- 1 Aug 2025 (estimated)
- Study completion
- 1 Aug 2025 (estimated)
- First posted
- 7 Jul 2021 (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.
Neostigmine is commonly used for medical treatment of acute colonic pseudo obstruction, however, the ideal route of administration has not been determined. Though IV push works rapidly, it is likely associated with the most side effects. This study will compare the efficacy and side effect profile of 2 potential routes of administration: IV push and subcutaneous.
Detailed description
Acute colonic pseudo-obstruction (ACPO) is a severe form of colonic ileus seen in patients hospitalized with a variety of medical and surgical conditions. The most serious complication is spontaneous colonic perforation, which occurs in 3% of cases with a mortality rate of up to 50%. The risk of perforation is greater in those patients with a cecal diameter >12 cm, although the duration of dilation might be more important than the cecal diameter. A significant number of patients will respond to the conservative measures enumerated in the abstract.
Endoscopic decompression of the dilated colon is undertaken commonly to prevent spontaneous perforation. However, it is performed under suboptimal conditions (unprepared and distended colon) increasing the risk of complications with a morbidity rate of 3% and a mortality rate of 1%. Furthermore, although effective initially in 69% of cases, 40% of them will have at least one recurrence. To decrease this recurrence rate, endoscopic placement of a drainage tube is now advocated. Patients who fail to respond to conservative therapy and colonoscopic decompression will require surgery, which has a mortality rate of up to 26%.
In an effort to find a more effective, noninvasive therapy, Ponec et al., introduced and highlighted the effect of IV neostigmine (2 mg over 3-5 min). Neostigmine was significantly more effective than placebo in rapidly decreasing colonic dilation in the majority of patients with ACPO. Although it has a short half-life, a single IV dose of 2 mg of neostigmine was sufficient in most cases to restore colonic motility.
It is important to be aware of contraindications to using parasympathetic agents, including bradyarrhythmia and history of bronchospasm. Patients need to be monitored while neostigmine is infused, and atropine should be available in the event of complications. Patients with renal insufficiency might be at higher risk of complications as a significant quantity of the drug is excreted in urine.
In light of these contraindications, administration by the subcutaneous (SQ) route has been utilized intermittently for ACPO. Data for use of SQ administration of neostigmine in adult patients are limited to one multi-institutional observational study, one case series, and two case reports in acute medical and palliative care patients. Although these case reports describe a range of dosing, the SQ route of administration appears to be attractive alternative to IV administration for this indication, with a time to effect of 8 to 10 hours.
This study is a prospective randomized non-inferiority trial that seeks to analyze the success of two different routes of neostigmine administration, sub-cutaneous and IV push, for safety and efficacy in the ACPO patient population.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Prospective randomized non-inferiority trial 2 Arms: 1. 1.0 mg subcutaneous repeated q8hr until resolution for up to 24 hours (3.0 mg total in 24 hours) 2. 2 mg slow intravenous injection over five minutes repeated q6hr until resolution for up to 24 hours. (8 mg total in 24 hours) (CONTROL GROUP)
| Arm | Type | Receives |
|---|---|---|
| IV push | Active comparator | Drug: Neostigmine2 mg slow intravenous injection over five minutes repeated q12hr until resolution for up to 24 hours. (4 mg total in 24 hours) |
| subcutaneous | Experimental | Drug: Neostigmine1.0 mg subcutaneous repeated q8hr until resolution for up to 24 hours (3.0 mg total in 24 hours) |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Patients with radiologically confirmed acute colonic pseudo obstruction (ACPO).
- Distal obstruction ruled out on imaging (Contrast enema, endoscopy, CT scan)
Key exclusion criteria (12 listed)
- Patients with previous neostigmine administration during current hospitalization
- Patients with prior attempt at endoscopic decompression on this admission.
- Patients with base-line heart rate of less than 60 beats per minute or on beta blocker medication
- Patients with systolic blood pressure of less than 90 mm Hg
- Signs of bowel perforation, with peritoneal signs on physical examination or free air on radiographs
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 |
|---|---|---|
| NeostigmineAlso: Bloxierz, Vagostigmin, Prostigmincholinesterase inhibitor | Drug | IV push, subcutaneous |
Primary outcome
Number of patients with radiographic resolution of colonic pseudo obstruction
Time frame: 24 hours
Number of patients who have cecal diameter <9 cm AND transverse diameter <6 cm on abdominal x-ray within 24h of initiation of neostigmine therapy.
2 secondary outcomes
Number of patients with recurrence of colonic pseudo obstruction
Time frame: 7 days
Number of patients with adverse medication reactions
Time frame: 24 hours
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2023.
- Background: PubMed 7973215DeMets DL, Lan KK. Interim analysis: the alpha spending function approach. Stat Med. 1994 Jul 15-30;13(13-14):1341-52; discussion 1353-6. doi: 10.1002/sim.4780131308.
- Background: PubMed 31083785Frankel A, Gillespie C, Lu CT, Hewett P, Wattchow D. Subcutaneous neostigmine appears safe and effective for acute colonic pseudo-obstruction (Ogilvie's syndrome). ANZ J Surg. 2019 Jun;89(6):700-705. doi: 10.1111/ans.15265. Epub 2019 May 13.
- Background: PubMed 10403850Ponec RJ, Saunders MD, Kimmey MB. Neostigmine for the treatment of acute colonic pseudo-obstruction. N Engl J Med. 1999 Jul 15;341(3):137-41. doi: 10.1056/NEJM199907153410301.
- Background: PubMed 29359574Kram B, Greenland M, Grant M, Campbell ME, Wells C, Sommer C. Efficacy and Safety of Subcutaneous Neostigmine for Ileus, Acute Colonic Pseudo-obstruction, or Refractory Constipation. Ann Pharmacother. 2018 Jun;52(6):505-512. doi: 10.1177/1060028018754302. Epub 2018 Jan 23.
- Background: PubMed 30541715Ilban O, Cicekci F, Celik JB, Bas MA, Duman A. Neostigmine treatment protocols applied in acute colonic pseudo-obstruction disease: A retrospective comparative study. Turk J Gastroenterol. 2019 Mar;30(3):228-233. doi: 10.5152/tjg.2018.18193.
- Background: PubMed 11430537van der Spoel JI, Oudemans-van Straaten HM, Stoutenbeek CP, Bosman RJ, Zandstra DF. Neostigmine resolves critical illness-related colonic ileus in intensive care patients with multiple organ failure--a prospective, double-blind, placebo-controlled trial. Intensive Care Med. 2001 May;27(5):822-7. doi: 10.1007/s001340100926.
- Background: PubMed 16306137Sgouros SN, Vlachogiannakos J, Vassiliadis K, Bergele C, Stefanidis G, Nastos H, Avgerinos A, Mantides A. Effect of polyethylene glycol electrolyte balanced solution on patients with acute colonic pseudo obstruction after resolution of colonic dilation: a prospective, randomised, placebo controlled trial. Gut. 2006 May;55(5):638-42. doi: 10.1136/gut.2005.082099. Epub 2005 Nov 23.
- Background: PubMed 27270510Vogel JD, Feingold DL, Stewart DB, Turner JS, Boutros M, Chun J, Steele SR. Clinical Practice Guidelines for Colon Volvulus and Acute Colonic Pseudo-Obstruction. Dis Colon Rectum. 2016 Jul;59(7):589-600. doi: 10.1097/DCR.0000000000000602. No abstract available.
- Individual participant dataSharing planned: No
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.
Meghan Lewis, MD principal investigator
University of Southern California
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 Neostigmine in people with Ogilvie Syndrome, run by University of Southern California 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 12 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: status not confirmed, as of the sponsor's last update on 25 Aug 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. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jordan Wlodarczyk, md (7143579599, jordan.wlodarczyk@med.usc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients with radiographic resolution of colonic pseudo obstruction (time frame: 24 hours). 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 NCT04951726, which also lists 8 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 25 Aug 2023.