search
Back to results

Remote Ischemic Preconditioning in Head and Neck Cancer Reconstruction - A Randomized Controlled Trial (RIPC-HNC)

Primary Purpose

Head and Neck Neoplasms

Status
Completed
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Remote ischemic preconditioning
Sham
Sponsored by
Aarhus University Hospital Skejby
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Head and Neck Neoplasms focused on measuring Head and Neck Neoplasms, Surgical Flaps, Ischemic Preconditioning, Hemostasis, Thrombosis, Immune System, Reperfusion Injury

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histologically verified or clinically suspected malignant tumor in the oral cavity, maxillae, mandible, pharynx, larynx, and/or esophagus.
  • Will undergo tumor resection and immediate free flap reconstruction at Aarhus University Hospital, Denmark.
  • The reconstruction is planned with a single free flap.

Exclusion Criteria:

  • Arterial and/or venous thromboembolism within the last three months.
  • The reconstruction is planned with more than one free flap.

Sites / Locations

  • Centre for Hemophilia and Thrombosis, Department of Clinical Biochemistry, Aarhus University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

Remote ischemic preconditioning

Sham

Arm Description

Four 5-minute cycles of upper extremity ischemia, each separated by five minutes of reperfusion. The treatment will be carried out with a tourniquet inflated to 200 mmHg during general anaesthesia prior to flap ischemia and transfer.

The tourniquet will be attached to the patient's upper extremity but never inflated.

Outcomes

Primary Outcome Measures

Acute effects on primary hemostasis: Reduced collagen-induced platelet aggregation in whole blood measured by the Multiplate Analyzer.

Secondary Outcome Measures

Acute effects on secondary hemostasis: Plasma samples will be analyzed by standard coagulation assays.
Acute effects on fibrinolysis: Plasma samples will be analyzed for markers of fibrinolysis.
Acute effects on global hemostasis: Plasma samples will be analyzed with the thrombin generation assay.
Acute effects on systemic inflammation: Plasma samples will be analyzed for complement, acute-phase proteins, cytokines, and leukocytes.
Effects on complication rates: Flap complications, systemic complications, morbidity and mortality.

Full Information

First Posted
September 9, 2015
Last Updated
March 2, 2018
Sponsor
Aarhus University Hospital Skejby
search

1. Study Identification

Unique Protocol Identification Number
NCT02548377
Brief Title
Remote Ischemic Preconditioning in Head and Neck Cancer Reconstruction - A Randomized Controlled Trial
Acronym
RIPC-HNC
Official Title
Remote Ischemic Preconditioning in Head and Neck Cancer Reconstruction - A Randomized Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
March 2018
Overall Recruitment Status
Completed
Study Start Date
September 29, 2015 (Actual)
Primary Completion Date
November 28, 2017 (Actual)
Study Completion Date
February 26, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Aarhus University Hospital Skejby

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of the trial is to investigate, if remote ischemic preconditioning reduces the risk of complications in patients undergoing resection of head and neck cancer and immediate reconstruction with autologous free tissue transfer. Remote ischemic preconditioning is a treatment, which is carried out by inducing brief episodes of upper arm occlusion using an inflatable tourniquet. Blood samples will be taken during the operation and postoperatively to evaluate the effects of remote ischemic preconditioning. These blood samples will be analyzed for clotting properties and markers of inflammation. Furthermore, effects on the blood supply of the transferred tissue flap will be measured by infrared thermography. Effects on surgical complication rates will be obtained by clinical follow-up and patient chart review.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head and Neck Neoplasms
Keywords
Head and Neck Neoplasms, Surgical Flaps, Ischemic Preconditioning, Hemostasis, Thrombosis, Immune System, Reperfusion Injury

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
60 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Remote ischemic preconditioning
Arm Type
Experimental
Arm Description
Four 5-minute cycles of upper extremity ischemia, each separated by five minutes of reperfusion. The treatment will be carried out with a tourniquet inflated to 200 mmHg during general anaesthesia prior to flap ischemia and transfer.
Arm Title
Sham
Arm Type
Sham Comparator
Arm Description
The tourniquet will be attached to the patient's upper extremity but never inflated.
Intervention Type
Procedure
Intervention Name(s)
Remote ischemic preconditioning
Intervention Type
Procedure
Intervention Name(s)
Sham
Primary Outcome Measure Information:
Title
Acute effects on primary hemostasis: Reduced collagen-induced platelet aggregation in whole blood measured by the Multiplate Analyzer.
Time Frame
Blood samples will be analyzed immediately. Data will be assessed and presented within five years.
Secondary Outcome Measure Information:
Title
Acute effects on secondary hemostasis: Plasma samples will be analyzed by standard coagulation assays.
Time Frame
Plasma samples will be analyzed immediately. Data will be assessed and presented within five years.
Title
Acute effects on fibrinolysis: Plasma samples will be analyzed for markers of fibrinolysis.
Time Frame
Data will be analyzed, assessed, and presented within five years.
Title
Acute effects on global hemostasis: Plasma samples will be analyzed with the thrombin generation assay.
Time Frame
Data will be analyzed, assessed, and presented within five years.
Title
Acute effects on systemic inflammation: Plasma samples will be analyzed for complement, acute-phase proteins, cytokines, and leukocytes.
Time Frame
Data will be analyzed, assessed, and presented within five years.
Title
Effects on complication rates: Flap complications, systemic complications, morbidity and mortality.
Time Frame
Follow-up is 30 days from the operation. Data will be obtained from visits to the outpatient clinic and by patient chart review. Data will be analyzed, assessed, and presented within five years.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically verified or clinically suspected malignant tumor in the oral cavity, maxillae, mandible, pharynx, larynx, and/or esophagus. Will undergo tumor resection and immediate free flap reconstruction at Aarhus University Hospital, Denmark. The reconstruction is planned with a single free flap. Exclusion Criteria: Arterial and/or venous thromboembolism within the last three months. The reconstruction is planned with more than one free flap.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anne-Mette Hvas, M.D., Ph.D.
Organizational Affiliation
Aarhus University Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Centre for Hemophilia and Thrombosis, Department of Clinical Biochemistry, Aarhus University Hospital
City
Aarhus N
ZIP/Postal Code
8200
Country
Denmark

12. IPD Sharing Statement

Citations:
PubMed Identifier
3567445
Citation
Taylor GI, Palmer JH. The vascular territories (angiosomes) of the body: experimental study and clinical applications. Br J Plast Surg. 1987 Mar;40(2):113-41. doi: 10.1016/0007-1226(87)90185-8.
Results Reference
background
PubMed Identifier
24281576
Citation
Chubb DP, Taylor GI, Ashton MW. True and 'choke' anastomoses between perforator angiosomes: part II. dynamic thermographic identification. Plast Reconstr Surg. 2013 Dec;132(6):1457-1464. doi: 10.1097/01.prs.0000434407.73390.82.
Results Reference
background
PubMed Identifier
22418714
Citation
Selber JC, Angel Soto-Miranda M, Liu J, Robb G. The survival curve: factors impacting the outcome of free flap take-backs. Plast Reconstr Surg. 2012 Jul;130(1):105-113. doi: 10.1097/PRS.0b013e318254b1b9.
Results Reference
background
PubMed Identifier
9727436
Citation
Khouri RK, Cooley BC, Kunselman AR, Landis JR, Yeramian P, Ingram D, Natarajan N, Benes CO, Wallemark C. A prospective study of microvascular free-flap surgery and outcome. Plast Reconstr Surg. 1998 Sep;102(3):711-21. doi: 10.1097/00006534-199809030-00015.
Results Reference
background
PubMed Identifier
17589253
Citation
Culliford AT 4th, Spector J, Blank A, Karp NS, Kasabian A, Levine JP. The fate of lower extremities with failed free flaps: a single institution's experience over 25 years. Ann Plast Surg. 2007 Jul;59(1):18-21; discussion 21-2. doi: 10.1097/01.sap.0000262740.34106.1b.
Results Reference
background
PubMed Identifier
11494394
Citation
Olsson E, Svartling N, Asko-Seljavaara S, Lassila R. Activation of coagulation and fibrinolysis during reconstructive microsurgery in patients with cancer. Microsurgery. 2001;21(5):208-13. doi: 10.1002/micr.1040.
Results Reference
background
PubMed Identifier
3769170
Citation
Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation. 1986 Nov;74(5):1124-36. doi: 10.1161/01.cir.74.5.1124.
Results Reference
background
PubMed Identifier
12460865
Citation
Kharbanda RK, Mortensen UM, White PA, Kristiansen SB, Schmidt MR, Hoschtitzky JA, Vogel M, Sorensen K, Redington AN, MacAllister R. Transient limb ischemia induces remote ischemic preconditioning in vivo. Circulation. 2002 Dec 3;106(23):2881-3. doi: 10.1161/01.cir.0000043806.51912.9b.
Results Reference
background
PubMed Identifier
17172279
Citation
Schmidt MR, Smerup M, Konstantinov IE, Shimizu M, Li J, Cheung M, White PA, Kristiansen SB, Sorensen K, Dzavik V, Redington AN, Kharbanda RK. Intermittent peripheral tissue ischemia during coronary ischemia reduces myocardial infarction through a KATP-dependent mechanism: first demonstration of remote ischemic perconditioning. Am J Physiol Heart Circ Physiol. 2007 Apr;292(4):H1883-90. doi: 10.1152/ajpheart.00617.2006. Epub 2006 Dec 15.
Results Reference
background
PubMed Identifier
15965583
Citation
Kerendi F, Kin H, Halkos ME, Jiang R, Zatta AJ, Zhao ZQ, Guyton RA, Vinten-Johansen J. Remote postconditioning. Brief renal ischemia and reperfusion applied before coronary artery reperfusion reduces myocardial infarct size via endogenous activation of adenosine receptors. Basic Res Cardiol. 2005 Sep;100(5):404-12. doi: 10.1007/s00395-005-0539-2. Epub 2005 Jun 17.
Results Reference
background
PubMed Identifier
20189026
Citation
Botker HE, Kharbanda R, Schmidt MR, Bottcher M, Kaltoft AK, Terkelsen CJ, Munk K, Andersen NH, Hansen TM, Trautner S, Lassen JF, Christiansen EH, Krusell LR, Kristensen SD, Thuesen L, Nielsen SS, Rehling M, Sorensen HT, Redington AN, Nielsen TT. Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial. Lancet. 2010 Feb 27;375(9716):727-34. doi: 10.1016/S0140-6736(09)62001-8.
Results Reference
background
PubMed Identifier
24203849
Citation
Hougaard KD, Hjort N, Zeidler D, Sorensen L, Norgaard A, Hansen TM, von Weitzel-Mudersbach P, Simonsen CZ, Damgaard D, Gottrup H, Svendsen K, Rasmussen PV, Ribe LR, Mikkelsen IK, Nagenthiraja K, Cho TH, Redington AN, Botker HE, Ostergaard L, Mouridsen K, Andersen G. Remote ischemic perconditioning as an adjunct therapy to thrombolysis in patients with acute ischemic stroke: a randomized trial. Stroke. 2014 Jan;45(1):159-67. doi: 10.1161/STROKEAHA.113.001346. Epub 2013 Nov 7.
Results Reference
background
PubMed Identifier
10436142
Citation
Dickson EW, Reinhardt CP, Renzi FP, Becker RC, Porcaro WA, Heard SO. Ischemic preconditioning may be transferable via whole blood transfusion: preliminary evidence. J Thromb Thrombolysis. 1999 Aug;8(2):123-9. doi: 10.1023/a:1008911101951.
Results Reference
background
PubMed Identifier
20449597
Citation
Lim SY, Yellon DM, Hausenloy DJ. The neural and humoral pathways in remote limb ischemic preconditioning. Basic Res Cardiol. 2010 Sep;105(5):651-5. doi: 10.1007/s00395-010-0099-y. Epub 2010 May 7.
Results Reference
background
PubMed Identifier
12791590
Citation
Addison PD, Neligan PC, Ashrafpour H, Khan A, Zhong A, Moses M, Forrest CR, Pang CY. Noninvasive remote ischemic preconditioning for global protection of skeletal muscle against infarction. Am J Physiol Heart Circ Physiol. 2003 Oct;285(4):H1435-43. doi: 10.1152/ajpheart.00106.2003. Epub 2003 Jun 5.
Results Reference
background
PubMed Identifier
22947090
Citation
Ropcke DM, Hjortdal VE, Toft GE, Jensen MO, Kristensen SD. Remote ischemic preconditioning reduces thrombus formation in the rat. J Thromb Haemost. 2012 Nov;10(11):2405-6. doi: 10.1111/j.1538-7836.2012.04914.x. No abstract available.
Results Reference
background
PubMed Identifier
21083644
Citation
Pedersen CM, Cruden NL, Schmidt MR, Lau C, Botker HE, Kharbanda RK, Newby DE. Remote ischemic preconditioning prevents systemic platelet activation associated with ischemia-reperfusion injury in humans. J Thromb Haemost. 2011 Feb;9(2):404-7. doi: 10.1111/j.1538-7836.2010.04142.x. No abstract available.
Results Reference
background
PubMed Identifier
1469751
Citation
Mounsey RA, Pang CY, Boyd JB, Forrest C. Augmentation of skeletal muscle survival in the latissimus dorsi porcine model using acute ischemic preconditioning. J Otolaryngol. 1992 Oct;21(5):315-20.
Results Reference
background
PubMed Identifier
12045567
Citation
Kuntscher MV, Schirmbeck EU, Menke H, Klar E, Gebhard MM, Germann G. Ischemic preconditioning by brief extremity ischemia before flap ischemia in a rat model. Plast Reconstr Surg. 2002 Jun;109(7):2398-404. doi: 10.1097/00006534-200206000-00034.
Results Reference
background
PubMed Identifier
12375286
Citation
Kuntscher MV, Kastell T, Sauerbier M, Nobiling R, Gebhard MM, Germann G. Acute remote ischemic preconditioning on a rat cremasteric muscle flap model. Microsurgery. 2002;22(6):221-6. doi: 10.1002/micr.10041.
Results Reference
background
PubMed Identifier
15458954
Citation
Moses MA, Addison PD, Neligan PC, Ashrafpour H, Huang N, Zair M, Rassuli A, Forrest CR, Grover GJ, Pang CY. Mitochondrial KATP channels in hindlimb remote ischemic preconditioning of skeletal muscle against infarction. Am J Physiol Heart Circ Physiol. 2005 Feb;288(2):H559-67. doi: 10.1152/ajpheart.00845.2004. Epub 2004 Sep 30.
Results Reference
background
PubMed Identifier
9788213
Citation
Restifo RJ, Thomson JG. The preconditioned TRAM flap: preliminary clinical experience. Ann Plast Surg. 1998 Oct;41(4):343-7. doi: 10.1097/00000637-199810000-00001.
Results Reference
background
PubMed Identifier
22111972
Citation
Kraemer R, Lorenzen J, Kabbani M, Herold C, Busche M, Vogt PM, Knobloch K. Acute effects of remote ischemic preconditioning on cutaneous microcirculation--a controlled prospective cohort study. BMC Surg. 2011 Nov 23;11:32. doi: 10.1186/1471-2482-11-32.
Results Reference
background
PubMed Identifier
25278482
Citation
Kolbenschlag J, Sogorski A, Harati K, Daigeler A, Wiebalck A, Lehnhardt M, Kapalschinski N, Goertz O. Upper extremity ischemia is superior to lower extremity ischemia for remote ischemic conditioning of antero-lateral thigh cutaneous blood flow. Microsurgery. 2015 Mar;35(3):211-7. doi: 10.1002/micr.22336. Epub 2014 Oct 3.
Results Reference
background

Learn more about this trial

Remote Ischemic Preconditioning in Head and Neck Cancer Reconstruction - A Randomized Controlled Trial

We'll reach out to this number within 24 hrs