RIPC-HNC: Remote Ischemic Preconditioning in Head and Neck Cancer Reconstruction - A Randomized Controlled Trial
Sponsor
Aarhus University Hospital Skejby (Other)
Overall Status
Completed
CT.gov ID
NCT02548377
Collaborator
(none)
60
1
2
28.9
2.1
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Study Design
Study Type:
Interventional
Actual Enrollment
:
60 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Participant)
Primary Purpose:
Treatment
Official Title:
Remote Ischemic Preconditioning in Head and Neck Cancer Reconstruction - A Randomized Controlled Trial
Actual Study Start Date
:
Sep 29, 2015
Actual Primary Completion Date
:
Nov 28, 2017
Actual Study Completion Date
:
Feb 26, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Remote ischemic preconditioning 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. |
Procedure: Remote ischemic preconditioning
|
| Sham Comparator: Sham The tourniquet will be attached to the patient's upper extremity but never inflated. |
Procedure: Sham
|
Outcome Measures
Primary Outcome Measures
- Acute effects on primary hemostasis: Reduced collagen-induced platelet aggregation in whole blood measured by the Multiplate Analyzer. [Blood samples will be analyzed immediately. Data will be assessed and presented within five years.]
Secondary Outcome Measures
- Acute effects on secondary hemostasis: Plasma samples will be analyzed by standard coagulation assays. [Plasma samples will be analyzed immediately. Data will be assessed and presented within five years.]
- Acute effects on fibrinolysis: Plasma samples will be analyzed for markers of fibrinolysis. [Data will be analyzed, assessed, and presented within five years.]
- Acute effects on global hemostasis: Plasma samples will be analyzed with the thrombin generation assay. [Data will be analyzed, assessed, and presented within five years.]
- Acute effects on systemic inflammation: Plasma samples will be analyzed for complement, acute-phase proteins, cytokines, and leukocytes. [Data will be analyzed, assessed, and presented within five years.]
- Effects on complication rates: Flap complications, systemic complications, morbidity and mortality. [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.]
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Centre for Hemophilia and Thrombosis, Department of Clinical Biochemistry, Aarhus University Hospital | Aarhus N | Denmark | 8200 |
Sponsors and Collaborators
- Aarhus University Hospital Skejby
Investigators
- Study Chair: Anne-Mette Hvas, M.D., Ph.D., Aarhus University Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
- 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. Epub 2003 Jun 5.
- Bøtker HE, Kharbanda R, Schmidt MR, Bøttcher 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, Sørensen 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.
- 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.
- 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.
- 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.
- Hougaard KD, Hjort N, Zeidler D, Sørensen L, Nørgaard 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, Bøtker HE, Østergaard 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.
- 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. Epub 2005 Jun 17.
- 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.
- 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.
- 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.
- 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.
- Küntscher 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.
- Küntscher 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.
- 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.
- 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. Epub 2004 Sep 30.
- 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.
- 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.
- 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.
- Pedersen CM, Cruden NL, Schmidt MR, Lau C, Bøtker 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.
- Restifo RJ, Thomson JG. The preconditioned TRAM flap: preliminary clinical experience. Ann Plast Surg. 1998 Oct;41(4):343-7.
- Røpcke 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.
- 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. Epub 2006 Dec 15.
- 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.
- 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.
Responsible Party:
Andreas Engel Krag,
M.D.,
Aarhus University Hospital Skejby
ClinicalTrials.gov Identifier:
NCT02548377
Other Study ID Numbers:
- RIPC-HNC
First Posted:
Sep 14, 2015
Last Update Posted:
Mar 5, 2018
Last Verified:
Mar 1, 2018
Keywords provided by Andreas Engel Krag,
M.D.,
Aarhus University Hospital Skejby
Additional relevant MeSH terms: