Injury of Body of PancreasPhase 2/3NCT02160808
Secretin Infusion to Prevent Pancreatic Leaks Following Pancreatic Resection
A Phase 2/3 study testing Secretin in people with Injury of Body of Pancreas, run by Dartmouth-Hitchcock Medical Center at 1 site in United States.
Trial summary
Pancreatic leaks complicate pancreatic resection in approximately 20% of cases. The pancreatic anastomosis or repair has been referred to as the Achilles heel of pancreatic surgery. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Injury of Body of Pancreas
- What is being tested?
- Secretin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 170 participants
- Where
- 1 siteUnited States
- Study dates
- May 2014to 21 Sep 2019
- Phase
- Phase 2/3
- 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 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Scheduled for pancreatic surgery requiring pancreatic resection at DHMC
- Age greater than 18 years old
- Ability to provide written informed consent
Who cannot join
- Inability to provide written informed consent
- Current ongoing acute pancreatitis
- Pregnant or nursing mothers
- Any medical condition which in the judgment of the Investigator renders participation in this study medically inadvisable.
- Participation in an investigational clinical study for a drug or medical device within 30 days prior to Visit 1.
Trial locations and contacts
1 site in 1 country.
United States1 site
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03756
About this study
Pancreatic leaks complicate pancreatic resection in approximately 20% of cases. The pancreatic anastomosis or repair has been referred to as the Achilles heel of pancreatic surgery. Unfortunately, despite recognition of this problem and multiple operative techniques proposed to prevent this complication, leaks continue to represent a major cause of morbidity for patients undergoing pancreatic surgery. Treatment of leaks often requires nutritional support with total parenteral nutrition to diminish the leak in addition to invasive interventions to contain the leak with drains, stents or in severe cases, reoperation. Experiential data suggest that intra-operative infusions of secretin, a naturally occurring hormone that stimulates bicarbonate release from the pancreas, following resection but just prior to abdomen closure, may identify a leak if present. If secretin can demonstrate evidence of leaking intra-operatively, the pancreatic duct leak may be able to be fixed prior to abdominal closure. The investigators aim to determine if giving an intra-operative infusion of secretin will allow for identification and treatment of leaks after pancreatic reconstruction and prior to abdominal closure, leading to a reduction in the rate of pancreatic anastomotic leaks requiring intervention. The investigators will perform a double-blind, randomized pilot study of 176 patients undergoing pancreatic resection (pancreaticoduodenectomy and distal pancreatectomy) at Dartmouth-Hitchcock Medical Center. 88 of those patients will receive an intra-operative secretin infusion prior to abdominal closure and 88 will receive a saline placebo. Our primary outcome of interest will be the rate of pancreas duct leaks in each group as measured by the concentration of amylase present in the surgical drains 3 days following surgery.
Read the detailed description
We hypothesize that intra-operative, intravenous secretin administration will decrease the rate of pancreatic leaks in patients undergoing pancreatic resection. Our primary objective is to determine if intravenous secretin administration will decrease the amount of pancreatic leaks as measured by the 2016 ISGPS definition of pancreatic leaks. Our 1) secondary objectives are to determine if intra-operative intravenous secretin administration changes the management of the pancreatic resection margin intra-operatively and 2) Length of hospital stay.
Use a level of detail similar to what would be used when submitting an article for publication in a peer reviewed journal. Explain the study procedures, data collection, and analysis process. Please define terms and explain concepts which might be confusing to reviewers who are not expert in the area of the study. If a formal protocol for the study exists, page references to the protocol are acceptable.
This study design is a prospective, double-blind, randomized-controlled trial. We will enroll patients in our institution undergoing pancreatic resection to receive either 1) one dose weight-based Secretin to be given once the closure of the pancreatic resection margin is complete 2) saline placebo.
Consent and basic demographics will be garnered by the physician in an office visit once the surgery has been scheduled and consent for the surgery is being obtained. The consent will be validated by the treating surgeon in the pre-procedure area on the day of the surgery.
The patient will undergo the scheduled surgery. Once the pancreatic anastomosis has been deemed acceptable by the attending physician, but prior to abdominal closure, the patient will be randomized to receive either Secretin (0.2 mcg/kg) or saline placebo. The attending surgeon will be blinded to this assignment.
10 minutes after receiving the Secretin or placebo, the attending surgeon will examine the anastomosis or repaired cut edge of the pancreas to determine if leakage of pancreatic fluid is noted, leak location(s), type (side branch/main duct) and whether any further intervention was performed in an effort to close the leak. Specifics of operative intervention will be documented. The patient will then undergo standard surgical closure of the abdomen.
As is standard of care at DHMC, surgical drains will be placed adjacent to the anastomosis and drain amylase output will be checked on POD #1, POD#3 and POD#5. Pancreatic leak is defined according to the International Study Group of Pancreatic Fistula (ISGPF) definition as amylase drainage of greater than a 3-fold elevation above the upper limit of normal in serum through the surgically placed drains on POD #3. Randomization assignments will be revealed once the patient has been discharged from the hospital following their initial surgical intervention. A follow-up visit with the patient two weeks following discharge, will evaluate for any evidence of ongoing pancreatic duct leak.
The primary outcome of interest will be the presence of pancreatic leaks based on the drain amylase on POD#3. Secondary outcomes will include the technical interventions intra-operatively directed to leak closure or manipulation of the anastomosis following Secretin or placebo stimulation and the length of hospitalization.
Patient demographics, risk factors, operative technique, randomization assignment and outcome data will be recorded on standard case report forms - See Case Report Forms in Appendix. Data will be stored in an encrypted hard-drive by a single agent (Gardner) who is the only researcher who has access to the randomization data.
- Conditions
- Injury of Body of Pancreas
- Being tested
- Secretin, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SecretinDrug
Drug to stimulate pancreatic secretion
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Secretin | Active comparator | Stimulate pancreatic secretion Receives: Drug: Secretin |
| Saline | Placebo comparator | Placebo should not stimulate the pancreas to release its fluids Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Biochemical Leak/Grade B Fistula/Grade C Fistula
Outcome based on revised ISGPS Guidelines which require a three day drain amylase concentration greater than 3x the normal serum amylase concentration. Biochemical leaks are the mildest for of fistula which have no clinical consequence. Grade B fistula are more severe requiring usually percutaneous drainage placement. Grade C fistula are most severe resulting in significant morbidity and/or death.
Measured: 3 days
Secondary outcomes (2)
Number of Participants With Intra-operative Intervention, Subsequent Biochemical Leak or B/C Fistula After Drug Administration
Following the administration of Secretin or Placebo intraoperatively, the surgeon will have the opportunity to evaluate the anastomosis to determine if there is ongoing leak. If there is ongoing leak, then the surgeon will be able to treat the leak intra-operatively prior to operative closure. In those patients in whom an intervention was performed, they were subsequently evaluated to determine if they developed a biochemical leak or grade B/C fistula.
Measured: Through completion of intra-operative intervention and subsequent biochemical leak, B/C Fistula up to 30 days post-operatively
Length of Hospitalization
Surrogate marker for operative success
Measured: Duration of study - average 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2014 (estimated)
- Study startMay 2014
- Primary completion21 Sep 2019
- Study completion21 Sep 2019
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 (1)Papers the sponsor has linked to this study.
- Other trials for Injury of Body of PancreasStudies of the same condition, open and under way.
- More trials run by Dartmouth-Hitchcock Medical CenterThe 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 170 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dartmouth-Hitchcock Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Timothy Gardner, Dartmouth-Hitchcock Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02160808
- Sponsor's protocol ID
- D13208 TBG-01
- Status last verified
- Mar 2020
- First submitted
- 13 May 2014
- Last updated
- 31 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Smith KD, Barth RJ, Colacchio TA, Chevalier JI, Bergmann LE, Purich ED, Gardner TB. Effect of intraoperative secretin on operative outcomes in pancreatic resection: A randomized controlled trial. Pancreatology. 2021 Apr;21(3):515-521. doi: 10.1016/j.pan.2021.02.002. Epub 2021 Feb 8.
PubMed 33602643
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Secretin Infusion to Prevent Pancreatic Leaks Following Pancreatic Resection
- ClinicalTrials.gov ID
- NCT02160808
- Acronym / sponsor ID
- D13208 TBG-01
- Conditions
- Injury of Body of Pancreas
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 170 participants (actual)
- Lead sponsor
- Dartmouth-Hitchcock Medical CenterUniversity, hospital or other
- Study start
- May 2014 (actual)
- Primary completion
- 21 Sep 2019 (actual)
- Study completion
- 21 Sep 2019 (actual)
- First posted
- 11 Jun 2014 (estimated)
- Results
- Posted 31 Mar 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Pancreatic leaks complicate pancreatic resection in approximately 20% of cases. The pancreatic anastomosis or repair has been referred to as the Achilles heel of pancreatic surgery. Unfortunately, despite recognition of this problem and multiple operative techniques proposed to prevent this complication, leaks continue to represent a major cause of morbidity for patients undergoing pancreatic surgery. Treatment of leaks often requires nutritional support with total parenteral nutrition to diminish the leak in addition to invasive interventions to contain the leak with drains, stents or in severe cases, reoperation. Experiential data suggest that intra-operative infusions of secretin, a naturally occurring hormone that stimulates bicarbonate release from the pancreas, following resection but just prior to abdomen closure, may identify a leak if present. If secretin can demonstrate evidence of leaking intra-operatively, the pancreatic duct leak may be able to be fixed prior to abdominal closure. The investigators aim to determine if giving an intra-operative infusion of secretin will allow for identification and treatment of leaks after pancreatic reconstruction and prior to abdominal closure, leading to a reduction in the rate of pancreatic anastomotic leaks requiring intervention. The investigators will perform a double-blind, randomized pilot study of 176 patients undergoing pancreatic resection (pancreaticoduodenectomy and distal pancreatectomy) at Dartmouth-Hitchcock Medical Center. 88 of those patients will receive an intra-operative secretin infusion prior to abdominal closure and 88 will receive a saline placebo. Our primary outcome of interest will be the rate of pancreas duct leaks in each group as measured by the concentration of amylase present in the surgical drains 3 days following surgery.
Detailed description
We hypothesize that intra-operative, intravenous secretin administration will decrease the rate of pancreatic leaks in patients undergoing pancreatic resection. Our primary objective is to determine if intravenous secretin administration will decrease the amount of pancreatic leaks as measured by the 2016 ISGPS definition of pancreatic leaks. Our 1) secondary objectives are to determine if intra-operative intravenous secretin administration changes the management of the pancreatic resection margin intra-operatively and 2) Length of hospital stay.
Use a level of detail similar to what would be used when submitting an article for publication in a peer reviewed journal. Explain the study procedures, data collection, and analysis process. Please define terms and explain concepts which might be confusing to reviewers who are not expert in the area of the study. If a formal protocol for the study exists, page references to the protocol are acceptable.
This study design is a prospective, double-blind, randomized-controlled trial. We will enroll patients in our institution undergoing pancreatic resection to receive either 1) one dose weight-based Secretin to be given once the closure of the pancreatic resection margin is complete 2) saline placebo.
Consent and basic demographics will be garnered by the physician in an office visit once the surgery has been scheduled and consent for the surgery is being obtained. The consent will be validated by the treating surgeon in the pre-procedure area on the day of the surgery.
The patient will undergo the scheduled surgery. Once the pancreatic anastomosis has been deemed acceptable by the attending physician, but prior to abdominal closure, the patient will be randomized to receive either Secretin (0.2 mcg/kg) or saline placebo. The attending surgeon will be blinded to this assignment.
10 minutes after receiving the Secretin or placebo, the attending surgeon will examine the anastomosis or repaired cut edge of the pancreas to determine if leakage of pancreatic fluid is noted, leak location(s), type (side branch/main duct) and whether any further intervention was performed in an effort to close the leak. Specifics of operative intervention will be documented. The patient will then undergo standard surgical closure of the abdomen.
As is standard of care at DHMC, surgical drains will be placed adjacent to the anastomosis and drain amylase output will be checked on POD #1, POD#3 and POD#5. Pancreatic leak is defined according to the International Study Group of Pancreatic Fistula (ISGPF) definition as amylase drainage of greater than a 3-fold elevation above the upper limit of normal in serum through the surgically placed drains on POD #3. Randomization assignments will be revealed once the patient has been discharged from the hospital following their initial surgical intervention. A follow-up visit with the patient two weeks following discharge, will evaluate for any evidence of ongoing pancreatic duct leak.
The primary outcome of interest will be the presence of pancreatic leaks based on the drain amylase on POD#3. Secondary outcomes will include the technical interventions intra-operatively directed to leak closure or manipulation of the anastomosis following Secretin or placebo stimulation and the length of hospitalization.
Patient demographics, risk factors, operative technique, randomization assignment and outcome data will be recorded on standard case report forms - See Case Report Forms in Appendix. Data will be stored in an encrypted hard-drive by a single agent (Gardner) who is the only researcher who has access to the randomization data.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Secretin | Active comparator | Drug: SecretinStimulate pancreatic secretion |
| Saline | Placebo comparator | Drug: PlaceboPlacebo should not stimulate the pancreas to release its fluids |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Scheduled for pancreatic surgery requiring pancreatic resection at DHMC
- Age greater than 18 years old
- Ability to provide written informed consent
Key exclusion criteria (5 listed)
- Inability to provide written informed consent
- Current ongoing acute pancreatitis
- Pregnant or nursing mothers
- Any medical condition which in the judgment of the Investigator renders participation in this study medically inadvisable.
- Participation in an investigational clinical study for a drug or medical device within 30 days prior to Visit 1.
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 |
|---|---|---|
| SecretinDrug to stimulate pancreatic secretion | Drug | Secretin |
| Placebo | Drug | Saline |
Primary outcome
Number of Participants With Biochemical Leak/Grade B Fistula/Grade C Fistula
Time frame: 3 days
Outcome based on revised ISGPS Guidelines which require a three day drain amylase concentration greater than 3x the normal serum amylase concentration. Biochemical leaks are the mildest for of fistula which have no clinical consequence. Grade B fistula are more severe requiring usually percutaneous drainage placement. Grade C fistula are most severe resulting in significant morbidity and/or death.
2 secondary outcomes
Number of Participants With Intra-operative Intervention, Subsequent Biochemical Leak or B/C Fistula After Drug Administration
Time frame: Through completion of intra-operative intervention and subsequent biochemical leak, B/C Fistula up to 30 days post-operatively
Length of Hospitalization
Time frame: Duration of study - average 30 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33602643Smith KD, Barth RJ, Colacchio TA, Chevalier JI, Bergmann LE, Purich ED, Gardner TB. Effect of intraoperative secretin on operative outcomes in pancreatic resection: A randomized controlled trial. Pancreatology. 2021 Apr;21(3):515-521. doi: 10.1016/j.pan.2021.02.002. Epub 2021 Feb 8.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Secretin in people with Injury of Body of Pancreas, run by Dartmouth-Hitchcock 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 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Mar 2020. 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Yes. Results are posted in the registry (first posted 31 Mar 2020). 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?
Number of Participants With Biochemical Leak/Grade B Fistula/Grade C Fistula (time frame: 3 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 NCT02160808, 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 31 Mar 2020.