Clinical trial NCT04005404
Conditions: Hip Fractures
Keywords: Regional Anesthesia Ultrasonography Hip Fractures Lumbosacral Plexus
Sponsor: Helios Research Center
Start date: 2019-08-05; Completion date: 2020-06-30
Enrollment: 80 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The study investigates whether treatment of proximal femoral fractures is possible using a peripheral regional anesthesia technique.

Detailed description:
The study investigates whether treatment of proximal femoral fractures is possible using a peripheral regional anesthesia technique.

After positioning on the non-fractured side, a double injection technique is used (dual guidance concept: nerve stimulation and sonography).

The injections are performed parasacrally (blockade of the sacral plexus under the piriformis muscle) and lumbar paravertebrally (psoas compartment block and transmuscular quadratus lumborum block). Per block 20 ml ropivacaine 0.375% is administered (total dose: 225mg ropivacaine).

The study examines the success rate (rate of successfully performed nerve blockade; need for supplemental medication: sufentanil and/or propofol; conversion rate to general anesthesia), circulatory stability (need for application of ephedrine or norepinephrine) and side effects.

Arms: arm 1: geriatric patients with intertrochanteric femoral fracture who have consented to the study intervention arm 2: geriatric patients with neck of femur fracture who have consented to the study intervention arm 3: geriatric patients with subtrochanteric femoral fracture who have consented to the study intervention
Interventions: intervention 1: Ropivacaine (sciatic nerve block) intervention 2: Ropivacaine (lumbar plexus block L2-L4) intervention 3: Ropivacaine (lumbar plexus block Th12-L1)
Intervention descriptions: intervention 1: injection of 20 ml ropivacaine 0.375% intervention 2: injection of 20 ml ropivacaine 0.375% intervention 3: injection of 20 ml ropivacaine 0.375%

Protocol documents:
Prot_000.pdf: 
 
1 
 
Study Protocol 
 
 
 
Ronald Seidel, MD  
Eduard Barbakov, MD 
HELIOS Medical Center Schwerin 
Department for Anesthesiology 
Wismarsche Strasse 393-7, DE-19049 Schwerin, Germany 
 
 
 
Title 
 
Surgical treatment of proximal femoral fractures under peripheral regional 
anesthesia. A prospective pilot study. 
 
ID: A 2018-0237 
NCT: 04005404 
 
 
Final Version 
 
 
Date 29.06.2019 
 
 
 
 
 
 
 
 
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2 
Study protocol (Summary) 
 
Title 
Surgical treatment of proximal femoral fractures under peripheral regional 
anesthesia. A prospective pilot study. 
 
Introduction 
Older multimorbid patients with hip fractures are a growing patient population due to 
demographic developments in western industrial nations. Hospital mortality increases 
with anesthesia risk and ranges from less than 1% (ASA (American Society of 
Anesthesiologists) Physical Status 1) to 50% (ASA PP 5). This presents the team 
with a number of challenges when patients are at high risk of anesthesia (ASA PP 3-
4, associated hospital mortality 5-20%). 
Surgical treatment can be performed under general or spinal anesthesia. Additional 
peripheral nerve blocks contribute to perioperative pain therapy.  
The aim of the study is to demonstrate that the surgical treatment of proximal femoral 
fractures is possible using a peripheral regional anesthesia procedure. 
Both spinal and general anesthesia can contribute to side effects such as 
postoperative delirium or circulatory instability. We postulate that these side effects 
occur less frequently when the procedure is performed under peripheral regional 
anesthesia.  
We perform a double injection technique (dual-guidance concept: ultrasound and 
nerve stimulation). The first injection targets the sacral plexus under the piriformis 
muscle.  
A second injection targets the lumbar plexus: psoas-compartment-block (segments 
L2-L4) and transmuscular quadratus-lumborum block (segments Th12-L1). 
 
Study design 
single-center, prospective 
 
Study goal 
anesthetic quality 
 
 
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Health economic goals 
 
We expect the study results to improve the safety of multimorbid elderly patients 
undergoing hip fracture surgery. 
 
Interventions  
 
 
 
 
 
 
 
 
Intervention A 
20ml ropivacaine 0.375% (parasacral sciatic nerve block)  
 
Intervention B 
20ml ropivacaine 0.375% (psoas-compartment block) 
 
Intervention C 
20ml ropivacaine 0.375% (transmuscular quadratus-lumborum 
 
 
 
block) 
 
Intervention D 
Supplemental analgesic (sufentanil) and/or sedative (propofol) 
medication 
 
Patient population 
Adult men and women undergoing surgical treatment of proximal femoral fractures. 
 
Study center 
HELIOS Medical Center Schwerin, Germany 
 
Schedule 
12-18 months 
 
 
 
 
 
 
 
 
 
 
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1. Introduction 
Both general and spinal anaesthesia are established anaesthesia procedures for the 
surgical treatment of proximal femoral fractures. Additional peripheral nerve 
blockades are performed with the aim of perioperative analgesia. 
 
2. Primary and secondary outcome parameters 
With the present prospective study design, we examine whether the surgical 
treatment of proximal femoral fractures exclusively under peripheral regional 
anesthesia (blockade of the lumbosacral plexus) is a reliable anesthesia procedure.  
The main objective is to determine the frequency of necessary supplementation by 
analgesics/sedatives (criterion 1) or the conversion rate (criterion 2) to general 
anaesthesia (infra- or supraglottic airway). Side effects (e.g. delirium and pneumonia 
rates), hospital length of stay and hospital mortality are recorded. 
 
3. Study design 
This is a single-center prospective study. 
 
4. Schedule 
The estimated recruitment schedule is approximately 12-18 months. 
 
5. Patient population 
5.1. Inclusion criteria 
The following inclusion criteria must be met : 
 
- Surgical treatment of proximal femoral fractures 
- Age over 18 years 
- Written informed consent 
 
5.2. Exclusion criteria 
Patients who meet one or more of the following criteria may not be included in the 
trial:  
- local and systemic signs of inflammation 
- known allergy to used local anaesthetics 
- Participation in other studies 
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- Obesity from grade 2 (BMI>35) 
- periprosthetic fractures- known persistent drug, drug or alcohol abuse 
 
5.3. Co-morbidities 
Preexisting co-morbidities are documented in the patient record.  
 
5.4. Co-medication 
All medications that are given in addition to the study medication are considered 
concomitant and are documented in the patient record (especially medications that 
have an inhibitory effect on the coagulation system). 
 
6. Study protocol 
6.1. Recruitment 
The patients are recruited in the context of anesthesiological preparation. Patients 
who have confirmed their participation in the exam by written informed consent will 
first be clinically evaluated. If the patient meets all inclusion and no exclusion criteria, 
the patient is enrolled in the study. 
 
6.2. Allocation of the study medication 
After admission to the study, each patient receives a patient number, which is noted 
on the Case Report Form (CRF).  
 
6.3. Monitoring and preoperative preparation 
Patients are initially treated in the context of normal preoperative preparation. This 
includes the installation of a peripheral-venous access with connection of 1000ml 
balanced electrolyte solution. After connection of an oxygen nasal probe (2 l/min 
oxygen) and administration of 5-10 µg Sufentanil the patients are placed on the non-
fractured side. 
 
The following parameters are monitored until complete postoperative recovery: 
 
- Blood pressure (NIBP) discontinuous 
- ECG continuous 
- SaO2 continuous 
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The parameters are documented in the anesthesia protocol. The minimum/maximum 
blood pressure and the need for circulatory drugs are recorded in the Patient 
Documentation Form. 
 
6.4. Interventions 
The ultrasound-guided regional anesthesia is performed by two experienced 
anesthetists. We use a Sonosite (EDGE) ultrasound device with convex transducer 
(C60 2-5MHz) and a Pajunk 21G-100mm Sonoplex needle in in-plane technique. At 
the same time, the needle position is confirmed by nerve stimulation (dual guidance 
concept). For this purpose we use a Stimuplex HNS12 from Braun, Melsungen, 
Germany (frequency 2Hz, pulse width 0.1ms, stimulation limit <1mA). 
Double injection technique with three (1a-c) target structures. (Resulting Anaesthesia 
level Th12-S3) 
 
 
 
 
 
 
 
 
Intervention 1a  
20ml Ropivacaine 0.375%. Parasacral ischiadicus block (18) 
 
 
 
Segments L4-S3  
 
Intervention 1b  
20ml Ropivacaine 0.375% Psoas compartment block (16) 
 
 
 
Segments L2-L4 
 
Intervention 1c  
20ml Ropivacaine 0.375% transmuscular quadratus-lumborum 
 
 
 
block (20) Segments T12-L1 
 
6.5. Follow-up 
Patients are initially cared for in the postoperative anesthesia care-unit (PACU). 
Depending on the clinical condition of the patients, further care is provided either at 
the normal ward or on an intensive care unit. For all study patients, a daily clinical 
visit is made until discharge. 
 
6.7. Health economic assessment 
Peripheral regional anesthesia expands the spectrum of possible anesthesia 
procedures for proximal femoral fractures. The procedure can contribute to the 
reduction of perioperative complications, especially in cases where there is a high 
risk of anesthesia. 
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7. Adverse events 
7.1. Adverse events due to the local anesthetic 
Allergic reaction 
Allergic reactions are very rare in amide-type topical anesthetics and are mostly due 
to the methylparaben preservative contained in larger packs (e.g., 50ml bottles). 
 
Local toxicity 
There are no major studies on local-toxic effects of prilocaine or ropivacaine. 
Possible would be a disturbance of the periaxonal milieu or the nervous blood supply 
(compartment effect of the local anesthetic depot). Neurological complications 
occurred after hyperbaric lidocaine was continuously administered intrathecally with 
7.5% glucose. Similar observations were not made for peripheral nerve blocks.  
 
Systemic toxicity 
Systemic toxicity occurs at high plasma levels by intravascular injection or absolute 
or relative overdose with rapid resorption of the local anesthetic from the site of 
action. 
The cerebral tendency to seizure is increased by the local anesthetic effect on 
inhibitory cortical centers. With or without preconvulsive warning signs (numbness of 
the tongue and perioral, metal taste, slurred speech, ear blades, blurred vision, 
restlessness), generalized convulsions occur. With rising plasma levels, coma and 
respiratory paralysis can occur. 
Inhibition of intracellular ATP production and blockade of sodium channels (vasal, 
cardiac, sympathetic) results in hypotension and variable cardiac arrhythmias 
(bradycardia to asystole, ventricular arrhythmias to ventricular fibrillation). 
 
7.2. Adverse events due to the peripheral nerve block 
Nerve lesions may be due to needle trauma (vascular or nerve lesion) or as a result 
of improper positioning on the operating table. In addition, side effects may occur as 
a result of the stress situation: vagally mediated bradycardias (syncope) or anxiety 
episodes with hypertonic and/or tachycardic circulatory conditions. 
 
 
 
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7.3. Evaluation of adverse events 
Ropivacaine is a drug approved for peripheral nerve blocks that we use within the 
maximum permitted dose and indication. All occurring complications are documented 
and the likelihood of the causal relationship with the regional anesthesia procedure is 
stated. Since this is a standard regional anaesthesia procedure, it can not be 
expected that previously unknown complications will occur. 
 
7.4. Information to the ethics committee 
In accordance with the GCP Regulation, any severe adverse event (SAE) or 
unexpected (SUSAR) adverse event occurring during the trial that could affect the 
safety of the subjects or the conduct of the trial will be reported to the relevant local 
ethics committee. The report is issued by the principal investigator. 
Non-serious adverse events are documented in the Patient Documentation Sheet 
(CRF) 
 
8. Dropout of patients 
The non-intervention-related reasons for a drop-out include in particular the 
withdrawal of the patient's consent and the subsequent disclosure of exclusion 
criteria (e.g. participation in another clinical trial). 
Drop-outs caused by the study intervention are e.g. severe cardiovascular 
complications (cardiac arrest, shock, threatening arrhythmias) due to the systemic 
toxicity of the local anaesthetic.  
If necessary, regional anesthesia is supplemented by the administration of 
analgesics and sedatives or general anesthesia is performed. The time and dose of 
the narcotics are documented and the procedure is performed as planned without the 
patient being excluded from the study.  
 
9. Statistical Analysis 
The statistical test methods are described in the statistical analysis plan.  
 
 
 
 
 
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10. Data management 
The investigator is responsible for the correct and complete entry of patient data into 
the case report form (CRF). A patient number (see 6.2.) is assigned to each patient 
on the CFR. The CRF is kept for 15 years. Any publication of data is anonymous.  
The patient will be informed by the investigator about the valid privacy policy. The 
patient will receive a copy of the privacy policy signed by the patient with place and 
date. The original is deposited in the study file.  
 
11. Ethical, legal and administrative aspects 
The investigator ensures that the test is performed in accordance with existing laws 
and regulations (ICH and GCP Guidelines, AMG). The study protocol and patient 
information are submitted to the Ethics Committee of the University of Rostock. 
Before starting the study, each patient must give written consent to the investigator, 
having previously been fully informed in an understandable manner about the nature, 
significance and scope of the clinical trial. The content of this information is 
documented on the consent form. The patient will be given a copy of the signed 
consent form. The original is deposited in the study file.  
 
12. Publication 
The aim is to publish the results of the study in a scientific journal. 
 
13. Sponsorship and conflict of interest 
The investigators declare no conflicts of interest. 
 
14. Amendments 
Any change to the study protocol will be substantiated and documented. The 
changes are considered part of the study protocol. 
 
 
 
 
 
 
 
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15. References 
 
1. 
Adhikary SD, Short AJ, El-Boghdadly K, et al (2018) Transmuscular quadratus 
lumborum versus lumbar plexus block for total hip arthroplasty: a retrospective 
propensity score matched cohort study. J Anaesthesiol Clin Pharmacol 
34:372-78  
 
2. 
Akkaya T, Comert A, Kendir A, et al (2008) Detailed anatomy of accessory 
obturator nerve blockade. Minerva Anestesiol 74:119-22 
 
3. 
Birnbaum K, Prescher A, Hessler S, et al (1997) The sensory innervation of 
the hip joint. An anatomical study. Surg Radiol Anat 19:371-5 
 
4. 
Coburn M, Sanders RD, Maze M, et al (2018) The hip fracture surgery in 
elderly patients (HIPELD) study to evaluate xenon anaesthesia for the 
prevention of postoperative delirium: a multicentre, randomized clinical trial. Br 
J Anaesth 120:127-37 
 
5. 
Duan X, Coburn M, Rossaint R, et al (2018) Efficacy of perioperative 
dexmedetomidine on postoperative delirium: systematic review and meta-
analysis with trial sequential analysis of randomised controlled trials. Br J 
Anaesth 121:384-97 
 
6. 
Giron-Arango L, Peng PWH, Chin KJ, et al (2018) Pericapsular nerve group 
(PENG) block for hip fracture. Reg Anesth Pain Med (in press) DOI: 
10.1097/AAP.0000000000000847 
 
7. 
Guay J, Parker MJ, Gajendragadkar PR, et al (2016) Anaesthesia for hip 
fracture surgery in adults (Review). Cochrane Database Syst Rev. DOI: 
10.1002/14651858.CD000521.pub3 
 
 
8. 
 Guay J, Parker MJ, Griffiths R, et al (2018)  Peripheral nerve blocks for hip 
fractures: a Cochrane Review. Anesth Analg 126:1695-1704 
 
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9. 
Johnston DF, Stafford M, McKinney M, et al (2016) Peripheral nerve blocks 
with sedation using propofol and alfentanil target-controlled infusion for hip 
fracture surgery: a review of 6 years in use. J Clin Anesth 29:33-39 
 
10. 
Kowark A, Adam C, Ahrens J, et al (2018). Improve hip fracture outcome in the 
elderly patient (iHOPE): a study protocol for a pragmatic, multicentre 
randomised controlled trial to test the efficacy of spinal versus general 
anaesthesia.  BMJ Open 8:e023609 DOI: 10.1136/bmjopen-2018-023609 
 
11. 
Lang J, Wachsmuth W (2004) Bein und Statik. In: Lanz T von, Wachsmuth W 
(Hrsg). Praktische Anatomie. Ein Lehr- und Hilfsbuch der anatomischen 
Grundlagen ärztlichen Handelns. Berlin: Springer; 73-91, 189  
 
12. 
Nielsen TD, Moriggl B, Søballe K, et al (2017)  A cadaveric study of 
ultrasound-guided subpectineal injectate spread around the obturator nerve 
and its hip articular branches. Reg Anaesth Pain Med 42:357-61 
 
 
13 
S1-Leitlinie Rückenmarksnahe Regionalanästhesien und 
 
Thromboembolieprophylaxe / antithrombotische Medikation (Juli 2014).  
 
Im Internet: www.awmf.org/uploads/tx_szleitlinien/001 
 
005l_S1_Rückenmarksnahe_Regionalanästhesie_Thromboembolieprophylax
 
e_2015-1.pdf; Stand: 31.07.2014 
 
14 
S2e-Leitlinie Schenkelhalsfraktur des Erwachsenen (Oktober 2015).  
 
Im Internet: www.awmf.org/uploads/tx_szleitlinien/012-
 
001l_S2e_Schenkelhalsfraktur_2015-10_01.pdf; Stand: 09.10.2015 
 
15. 
Sa M, Graca R, Reis H, et al (2018) Superior gluteal nerve: an new block on 
the block? Rev Bras Anestesiol 68:400-03 
 
16. 
Sauter AR, Ullensvang K, Niemi G, et al (2015) The Shamrock lumbar plexus 
block: a dose-finding study. Eur J Anaesthesiol 32:764-70 
 
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17. 
Short AJ, Barnett JJG, Gofeld M, et al (2018) Anatomic study of innervation of 
the anterior hip capsule: implication for image-guided intervention. Reg Anesth 
Pain Med 43:186-92 
 
18. 
Taha AM (2012) A simple and successful sonographic technique to identify the 
sciatic nerve in the parasacral area. Can J Anaesth 59:263-67 
 
19. 
Ting L, Joyce Y, Jun L, et al (2017) Comparison of regional with general 
anaesthesia on postoperative delirium (RAGA-delirium) in the older patients 
undergoing hip fracture surgery: study protocol for a multicentre randomised 
controlled trial. BMJ Open 7:e016937. DOI: 10.1136/bmjopen-2017-016937 
 
20. 
Ueshima H, Otake H, Lin JA (2017) Ultrasound-guided quadratus lumborum 
block: an updated review of anatomy and techniques. Biomed Res Int 
2017:2752876 DOI: 10.1155/2017/2752876 
 
21. 
Van Waesberghe J, Stevanovic A, Rossaint R, et al (2017) General vs. 
neuraxial anaesthesia in hip fracture patients: a systematic review and meta-
analysis. BMC Anesthesiol 28:87. DOI: 10.1186/s12871-017-0380-9 
 
22. 
White SM, Moppett IK, Griffiths R et al (2016) Secondary analysis of outcomes 
after 11085 hip fracture operations from the prospective UK Anaesthesia 
Sprint Audit of Practice (ASAP-2). Anaesthesia 71:506-14 
 
16. Responsibilities 
Ronald Seidel, MD  
Principal investigator 
Eduard Barbakow, MD 
Investigator 
 
17. Attachements 
Attachement 1 
 
Informed Consent Form 
Attachement 2 
 
Case Report Form 
 
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SAP_001.pdf: 
Statistical Analysis Plan 
 
 
 
Ronald Seidel, MD  
Eduard Barbakov, MD 
HELIOS Medical Center Schwerin 
Department for Anesthesiology 
Wismarsche Strasse 393-7, DE-19049 Schwerin, Germany 
 
 
 
Title 
 
Surgical treatment of proximal femoral fractures under peripheral regional 
anesthesia. A prospective pilot study. 
 
ID: A 2018-0237 
NCT: 04005404 
 
 
Final Version 
 
 
Date 29.06.2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan 
 
The metric parameters are described by mean value (Mw) and standard deviation 
(Sd). The Mann-Whitney U test tests whether the two groups differ in the distribution 
of the parameter. If the p-value of the test is less than the selected significance level 
(0.05), then the groups differ significantly in terms of distribution. 
 
Categorical parameters (0/1) are described by the exact Fisher test. The exact Fisher 
test examines whether each parameter is independent of its membership in a group. 
If the p-value of the test is less than the selected significance level (0.05), then there 
is a significant dependence. The two groups then differ significantly with respect to 
the selected parameter. 
 
The incidence of adverse events in the two groups is described with odds ratios (95% 
confidence interval). 
 
Statistical analyses were performed bilaterally, using GraphPad PRISM 8.0 
(GraphPad Software Inc., San Diego, CA, USA).