Clinical trial NCT02862912
Conditions: Adverse Reaction to Spinal Anesthetic Maternal Care for Cervical Incompetence
Keywords: Chloroprocaine cervical cerclage spinal anesthesia Bupivacaine
Sponsor: Columbia University
Start date: 2016-11-08; Completion date: 2020-01-31
Enrollment: 43 participants; Allocation: RANDOMIZED; Intervention model: FACTORIAL

Brief summary:
This study aims to determine whether or not spinal anesthesia with the local anesthetic drug, chloroprocaine, wears off faster than the local anesthetic drug, bupivacaine, and results in faster discharge from the post-anesthesia care unit after surgery.

Detailed description:
This will be a prospective, randomized, double blind clinical trial. Subjects will be ASA I and II women ≥18 yrs old with a singleton pregnancy in the 1st or 2nd trimester of pregnancy undergoing cervical cerclage with spinal anesthesia. Patients will be randomly allocated to the chloroprocaine (CP) or bupivacaine group (BUP). Patients will receive spinal anesthesia with either chloroprocaine 50 mg with fentanyl 15 mcg or bupivacaine 9 mg with fentanyl 15 mcg.

Bupivacaine is the most common local anesthetic used for cervical cerclage with spinal anesthesia. Bupivacaine is safe and has been preferred over other medications such as lidocaine, because it is associated with a low incidence of a complication from spinal anesthesia known as "transient neurologic symptoms" - a condition where pain and cramping in the buttocks and lower extremities can be experienced for several days. Bupivacaine is a long-acting local anesthetic agent and therefore has the disadvantage of a prolonged anesthetic recovery that may last a few hours.

Chloroprocaine is a local anesthetic with a fast onset and short duration that may be used for spinal anesthesia for ambulatory procedures. Chloroprocaine is currently used at the research institution for spinal anesthesia for ambulatory surgical patients, especially for lower extremity orthopedic procedures such as knee arthroscopy, as well as for pregnant patients.

Arms: arm 1: Patients in CP group will receive 3% 2-chloroprocaine 50 mg (1.67 ml) and fentanyl 15 mcg (0.3 ml) arm 2: Patients in BUP group will receive hyperbaric 0.75% bupivacaine 9 mg (1.4 ml), with fentanyl 15 mcg (0.3 ml), with saline (0.3 ml) to bring the volume to \~ 2 ml
Interventions: intervention 1: Chloroprocaine intervention 2: Bupivacaine intervention 3: Fentanyl intervention 4: Saline
Intervention descriptions: intervention 1: Administered as a single injection or continuously through an indwelling catheter - 50 mg intervention 2: A dextrose Solution is usually given as an injection - 9 mg (1.4 ml) intervention 3: 15 mcg Fentanyl will be included int he spinal anesthetic in both groups intervention 4: Preservative free normal saline (0.3 ml) to bring the volume to \~ 2 ml

Protocol documents:
Prot_SAP_001.pdf: 
 
 
  
Is the purpose of this submission to obtain a "Not Human Subjects Research" determination?
No
 
 
Enrollment status:
Open to enrollment or ongoing review of records/specimens
Provide any additional information necessary to explain the study status:
We have added the clinicaltrials.gov number--should have been added before
Since the last renewal:
Have there been any changes in the relevant literature that would affect the study design or procedures?
No
Have there been any interim findings associated with this study?
No
Have there been any publications resulting from this study?
No
Have any participants been enrolled using the Short Form process?
No
Is there a Data Monitoring Committee (DMC), Data Safety Monitoring Board (DSMB), or other monitoring entity
for this study?
No
Is an annual Progress Report required by the funding organization or coordinating center for this study?
No
Does this submission include a modification?
Yes
Provide a description of, and explanation for, all changes being proposed in this submission:
change in personnel.  Feloows Zheng and Shatil have left Columbia.  New Fellows Bernstein and Daoud are
added to protocol, Of note, we continue to be told that Dr. Bernstein does not have the "FDA part" of her RASCAL
exams when we add her to IRB protocols, but we have repeatedly sent her certificate to the IRB--not sure what the
problem is 
Indicate which sections of the Rascal submission are affected by the proposed modification. Each marked
section must be revised as part of this submission:
Columbia University Human Subjects Protocol Data Sheet
General Information
Protocol:
AAAQ0916(M00Y05)
Protocol Status:
Approved
Effective Date:
11/13/2019
Expiration Date:
11/12/2020
Originating Department Code:
ANE Anesthesiology (751000X)
Principal Investigator:
Smiley, Richard (rms7)
From what Columbia campus does this research
originate:
Medical Center
Title:
Chloroprocaine versus bupivacaine spinal anesthesia for cervical cerclage
Protocol Version #:
1
Abbreviated Title:
Chloroprocaine for cerclage
Was this protocol previously assigned a number by an IRB:
No
Renewal Information
[  ]General Information
[  ]Exempt and Expedited
[  ]Attributes
[x]Personnel
IRB-AAAQ0916
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Has the consent form been revised in this submission?
No
Does this submission include a report of a protocol violation?
No
 
 
Special review type: Check all that apply or check "None of the Above" box.
[  ]Review for 45 CFR 46.118 Determination (involvement of human subjects is anticipated but is not yet defined)
[  ]Funding review for Administrative IRB approval (such as for Center or Training Grants)
[x]None of the above
  
IRB of record information: Will a Columbia IRB be the IRB that is responsible for providing review, approval, and
oversight for this study?
Yes
Select the most appropriate response:
Columbia will be the IRB of record for the study procedures conducted by Columbia researchers (Note: this
response will apply to most submissions).
  
Is this research part of a multicenter study?
No
  
Please indicate if any of the following University resources are utilized:
[  ]  Cancer Center Clinical Protocol Data Management Compliance Core (CPDM)
[  ]  CTSA-Irving Institute Clinical Research Resource (CRR)
[  ]  CTSA- Irving Institute Columbia Community Partnership for Health (CCPH)
[x]  None of the above
 
 
Abbreviated Submission:
The IRB has an abbreviated submission process for multicenter studies supported by industry or NIH
cooperative groups (e.g., ACTG, HVTN, NCI oncology group studies, etc.), and other studies that have a complete
stand-alone protocol. The process requires completion of all Rascal fields that provide information regarding
local implementation of the study. However, entering study information into all of the relevant Rascal fields is not
required, as the Columbia IRBs will rely on the attached stand-alone (e.g., sponsor's) protocol for review of the
overall objectives.
If you select the Abbreviated Submission checkbox and a section is not covered by the attached stand-alone
protocol, you will need to go back and provide this information in your submission. 
[  ]Funding
[  ]Background
[  ]Research Aims and Abstracts
[  ]Procedures
[  ]Locations
[  ]Subjects
[  ]Data Security and Privacy
[  ]Risks/Benefits/Monitoring
[  ]Informed Consent/Recruitment
[  ]Attachments (including Rascal-generated attachments)
[  ]No revisions to submission content required
Attributes
Background
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Study Purpose and Rationale:
Provide pertinent background description with references that are related to the need to conduct this study. If
this is a clinical trial, the background should include both preclinical and clinical data. Be brief and to the point.
[  ]  Abbreviated Submission - This information is included in an attached stand-alone protocol. Proceed to the next
question
Cervical insufficiency, defined as the inability of the uterine cervix to retain a pregnancy in the
second trimester, in the absence of uterine contractions,1 affects 1% of the obstetric population
(about 1 in 500 pregnancies)2 and 8% of populations with recurrent miscarriages and mid-trimester
pregnancy losses.3 Cervical cerclage is a surgical procedure performed via the vaginal route,
whereby a suture is inserted at the junction of vagina and cervix, at the level of the internal os of
the cervix, to provide mechanical support and prevent preterm birth. The procedure is usually
performed as an elective outpatient procedure with a duration of approximately 30 minutes, but
occasionally is performed as an emergency, in the case of threatened miscarriage. An anesthetic
technique with a relatively short duration of action and recovery is indicated. Both regional and
general anesthesia have been successfully used;2 however spinal anesthesia is now
overwhelmingly the choice, as it has the advantage of preserving maternal airway reflexes and
limiting fetal exposure to anesthetic agents (although the procedure is usually performed beyond
the stage of highest teratogenicity risk). Throughout most of the 1990s, lidocaine was the
intrathecal local anesthetic agent of choice for these procedures, but fell out of favor because of
the frequency of reports of transient neurologic symptoms (TNS)- the reported incidence ranges
from 10 – 40%.4-6 Patients with TNS experience cramping, aching, or lancinating pain affecting the
lower extremities and buttocks. Symptoms, which may have variable severity, occur within 6 - 36
hours after spinal anesthesia and last between 1 – 7 days. Bupivacaine is now the most common
local anesthetic used for this procedure. Bupivacaine is associated with far less TNS but is a long-
acting agent and carries the disadvantage of a prolonged anesthetic recovery, which is a source of
significant patient dissatisfaction and impacts staffing and resources due to unnecessarily long
post-anesthesia care unit (PACU) stays. In our practice at CUMC, with typical dosing of intrathecal
hyperbaric bupivacaine 0.75% ranging from 7.5 – 9 mg, usually in conjunction with fentanyl 10 –
20 mcg, patients sometimes spend 5 hours or more in the PACU after a 30-minute outpatient
cervical cerclage procedure. These prolonged stays are partly a consequence of the CUMC
practice that maintains that patients must be able to void and ambulate independently prior to
discharge home, due to concerns about the risk of falls and readmission for urinary
retention. Chloroprocaine (2-chloroprocaine, CP) is an amino-ester local anesthetic with a fast
onset and short duration that has made a resurgence for use in spinal anesthesia for ambulatory
procedures.7 Although safe reports of its use for spinal anesthesia were published following its
introduction in 1952,8 CP was never widely adopted, probably due to the availability of lidocaine,
which had been introduced in 1949. The drug has had widespread use for epidural anesthesia,
and due to its rapid onset and low systemic toxicity, is considered to be critical for the safe practice
of obstetric anesthesiology (including at CUMC) for use in emergencies such as “stat” cesarean
sections in women with epidural catheters in place for labor anlagesia. Serious concerns about the
safety of the use of CP intrathecally arose in the wake of a series of case reports in the 1980’s of
catastrophic neurologic sequelae, such as adhesive arachnoiditis, following the injection of large
doses of the drug (average 611 mg) that had been meant to be injected into the epidural space.9-
11 Neurotoxicity was attributed to the preservative sodium bisulphite, which was hypothesized to
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provoke the release of sulphur dioxide, in the presence of the low pH of CP. Animal studies have
been inconclusive, with conflicting results believed to be related to interspecies variation in levels
of sulfur oxidase (catalyzes sulfites to sulfates), although variable results have also been seen in
studies involving the same species.12 The current formulation of CP has no additives. Vaghadia et
al.13 performed a recent trial involving 40 patients randomized to undergo transurethral resection
of the prostate with spinal anesthesia with either preservative free CP or lidocaine. Several
patients in the lidocaine group experienced TNS, and notably one patient in the CP group
developed an incomplete cauda equina syndrome that developed 24 hours later and persisted for
several weeks. The cause of that unfortunate complication is unclear. Contemporary reports of use
spinal CP began to reappear in small studies in volunteers in the mid-2000’s and then larger
studies followed, investigating its properties, such as minimum effective dose, and behavior with
added dextrose and clonidine, as well as comparisons with bupivacaine and lidocaine.14-26 This
work supports the safety of the use of spinal CP, demonstrates the low incidence of TNS and
particular suitability for surgeries in an ambulatory practice setting. CP is currently used very
frequently at CUMC for spinal anesthesia for ambulatory surgical patients, especially for lower
extremity orthopedic procedures such as knee arthroscopy. A CUMC Anesthesiology Department
review of CUMC practice between 2009 – 2014 reported 412 cases of CP use for spinal
anesthesia, with no associated complications. 27 A randomized controlled trial of spinal anesthesia
with bupivacaine or 2-chloroprocaine during cesarean section was recently published; the authors
reported no difference in time to motor block resolution among groups, but a more predictable
recovery was noted with 2-chloroprocaine.28 There are no published reports of the use of CP for
spinal anesthesia for cervical cerclage or other outpatient procedures in obstetric population. We
plan to perform a study in which patients undergoing cervical cerclage with spinal anesthesia will
be randomized to receive either plain 3% 2-chloroprocaine 50 mg or hyperbaric bupivacaine
9mg in conjunction with 15 mcg fentanyl. Our hypothesis is that the use of CP for outpatient spinal
anesthesia for cervical cerclage will lead to faster recovery of motor and sensory function than
bupivacaine spinal anesthesia, which is currently the customary practice at CUMC. Between 5 - 10
cervical cerclage procedures are performed each month on the CHONY labor and delivery floor.
We believe CP spinal anesthesia, compared with the bupivacaine spinal anesthesia, will result in
higher patient and higher staff satisfaction, and potentially economic benefits associated with
earlier PACU discharge and decreased nursing staff workload.      References: 1.         ACOG
Practice Bulletin No.142: Cerclage for the management of cervical insufficiency. Obstetrics and
gynecology 2014;123:372-9.2.         Ioscovich A, Popov A, Gimelfarb Y, et al. Anesthetic
management of prophylactic cervical cerclage: a retrospective multicenter cohort study. Archives
of gynecology and obstetrics 2015;291:509-12.3.         Alfirevic Z, Stampalija T, Roberts D,
Jorgensen AL. Cervical stitch (cerclage) for preventing preterm birth in singleton pregnancy. The
Cochrane database of systematic reviews 2012;4:CD008991.4.         Schneider M, Ettlin T,
Kaufmann M, et al. Transient neurologic toxicity after hyperbaric subarachnoid anesthesia with 5%
lidocaine. Anesthesia and analgesia 1993;76:1154-7.5.         Tarkkila P, Huhtala J, Tuominen M.
Transient radicular irritation after spinal anaesthesia with hyperbaric 5% lignocaine. British journal
of anaesthesia 1995;74:328-9.6.         Freedman JM, Li DK, Drasner K, Jaskela MC, Larsen B, Wi
S. Transient neurologic symptoms after spinal anesthesia: an epidemiologic study of 1,863
patients. Anesthesiology 1998;89:633-41.7.         Goldblum E, Atchabahian A. The use of 2-
chloroprocaine for spinal anaesthesia. Acta anaesthesiologica Scandinavica 2013;57:545-52.
8.         Foldes FF, Mc NP. 2-Chloroprocaine: a new local anesthetic agent. Anesthesiology
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1952;13:287-96.9.         Reisner LS, Hochman BN, Plumer MH. Persistent neurologic deficit and
adhesive arachnoiditis following intrathecal 2-chloroprocaine injection. Anesthesia and analgesia
1980;59:452-4.10.       Ravindran RS, Turner MS, Muller J. Neurologic effects of subarachnoid
administration of 2-chloroprocaine-CE, bupivacaine, and low pH normal saline in dogs. Anesthesia
and analgesia 1982;61:279-83.11.       Moore DC, Spierdijk J, vanKleef JD, Coleman RL, Love GF.
Chloroprocaine neurotoxicity: four additional cases. Anesthesia and analgesia 1982;61:155-9.
12.       Pollock JE. Intrathecal chloroprocaine--not yet "safe" by US FDA parameters. International
anesthesiology clinics 2012;50:93-100.13.       Vaghadia H, Neilson G, Lennox PH. Selective spinal
anesthesia for outpatient transurethral prostatectomy (TURP): randomized controlled comparison
of chloroprocaine with lidocaine. Acta anaesthesiologica Scandinavica 2012;56:217-23.14.      
Kouri ME, Kopacz DJ. Spinal 2-chloroprocaine: a comparison with lidocaine in volunteers.
Anesthesia and analgesia 2004;98:75-80, table of contents.15.       Warren DT, Kopacz DJ. Spinal
2-chloroprocaine: the effect of added dextrose. Anesthesia and analgesia 2004;98:95-101, table of
contents.16.       Vath JS, Kopacz DJ. Spinal 2-chloroprocaine: the effect of added fentanyl.
Anesthesia and analgesia 2004;98:89-94, table of contents.17.       Smith KN, Kopacz DJ,
McDonald SB. Spinal 2-chloroprocaine: a dose-ranging study and the effect of added epinephrine.
Anesthesia and analgesia 2004;98:81-8, table of contents.18.       Davis BR, Kopacz DJ. Spinal 2-
chloroprocaine: the effect of added clonidine. Anesthesia and analgesia 2005;100:559-65.19.      
Gonter AF, Kopacz DJ. Spinal 2-chloroprocaine: a comparison with procaine in volunteers.
Anesthesia and analgesia 2005;100:573-9.20.       Kopacz DJ. Spinal 2-chloroprocaine: minimum
effective dose. Regional anesthesia and pain medicine 2005;30:36-42.21.       Casati A, Danelli G,
Berti M, et al. Intrathecal 2-chloroprocaine for lower limb outpatient surgery: a prospective,
randomized, double-blind, clinical evaluation. Anesthesia and analgesia 2006;103:234-8, table of
contents.22.       Casati A, Fanelli G, Danelli G, et al. Spinal anesthesia with lidocaine or
preservative-free 2-chlorprocaine for outpatient knee arthroscopy: a prospective, randomized,
double-blind comparison. Anesthesia and analgesia 2007;104:959-64.23.       Camponovo C, Wulf
H, Ghisi D, et al. Intrathecal 1% 2-chloroprocaine vs. 0.5% bupivacaine in ambulatory surgery: a
prospective, observer-blinded, randomised, controlled trial. Acta anaesthesiologica Scandinavica
2014;58:560-6.24.       Yoos JR, Kopacz DJ. Spinal 2-chloroprocaine for surgery: an initial 10-
month experience. Anesthesia and analgesia 2005;100:553-8.25.       Yoos JR, Kopacz DJ. Spinal
2-chloroprocaine: a comparison with small-dose bupivacaine in volunteers. Anesthesia and
analgesia 2005;100:566-72.26.       Hejtmanek MR, Pollock JE. Chloroprocaine for spinal
anesthesia: a retrospective analysis. Acta anaesthesiologica Scandinavica 2011;55:267-72.
27.       Ivie R, Fu P, Maniker R. Chloroprocaine Spinal Compared to General Anesthesia for
Outpatient Knee Arthroscopy.  40th Annual Regional Anesthesiology and Acute Pain Meeting. Las
Vegas, Nevada  2015.28.        Maes S, Laubach M, Poelaert J. Randomised controlled trial of
spinal anaesthesia with bupivacaine or 2-chloroprocaine during caesarean section. Acta
anaesthesiologica Scandinavica 2015; Nov 26. [Epub ahead of print]
 
   
  
Study Design:
Describe the methodology that will be used in this study, covering such factors as retrospective vs. prospective
data collection, interventional vs. non-interventional, randomized vs. non-randomized, observational,
experimental, ethnography, etc.
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[  ]  Abbreviated Submission - This information is included in an attached stand-alone protocol. Proceed to the next
question
This will be a prospective, randomized, double blind clinical trial. Subjects will be ASA I and II
women 18 yrs old with singleton pregnancy in the 1st or 2nd trimester of pregnancy undergoing
cervical cerclage with spinal anesthesia. Patients will be randomly allocated to the chloroprocaine
(CP) or bupivacaine group (BUP). Patients will receive spinal anesthesia with either chloroprocaine
50 mg with fentanyl 15 mcg or bupivacaine 9 mg with fentanyl 15 mcg. The onset and resolution of
sensory and motor blockade, and time to achieve PACU discharge criteria, as well as patient
comfort and satisfaction with the procedure will be closely evaluated. The following day, patients
will be telephoned by an investigator to inquire about their satisfaction with their anesthesia and
the incidence of TNS symptoms, back pain and postdural puncture headache. 
  
Statistical Procedures:
Provide sufficient details so that the adequacy of the statistical procedures can be evaluated including power
calculations to justify the number of participants to be enrolled into the study. Definitions of subject terms such
as enrolled and accrued as used for Rascal submissions can be found in the Subjects section.
[  ]  Abbreviated Submission - This information is included in an attached stand-alone protocol. Proceed to the next
question
The null hypothesis is that there is no difference in recovery of sensory and motor function
between CP 50 mg + fentanyl 15 mcg and bupivacaine 9mg + fentanyl 15 mcg. Our primary
outcome will be mean time from spinal injection (tIT) to time to no motor block (t motor) (i.e. (t IT- t
motor), which corresponds to PACU discharge readiness. Previous studies of outpatient surgical
procedures suggest that this time is 200 - 300 minutes (SD ~ 50 min) with bupivacaine, 150 - 200
minutes with lidocaine and 150 minutes with CP, with standard deviations (when reported)
averaging about 10 - 20% of the values.[References: 1, 2, 3]
 
We will consider a difference between groups of 45 minutes to be clinically significant. Secondary
outcomes will include the time from intrathecal injection to time to ambulate (tIT - t amb) and void
(tIT - t void) (CUMC discharge criteria), rating of intraoperative discomfort, and incidence of TNS.
To reliably detect a 45 minute difference with a 25% standard deviation (e.g., 225 +/- 56.25 versus
180 +/- 45 minutes) with 80% power and an alpha of 0.05 will require 21 subjects per group. We
will recruit 25 per group to account for dropouts (expected to be low) and the possibility of non-
normal data. In reality, we expect a greater difference than 45 minutes between groups, and
believe the study is well-powered to find a clinically significant difference.
References:
    1.  Camponovo C, Wulf H, Ghisi D, et al. Intrathecal 1% 2-chloroprocaine vs. 0.5% bupivacaine
in ambulatory surgery: a prospective, observer-blinded, randomised, controlled trial. Acta
anaesthesiologica Scandinavica 2014;58:560-6.
    2.   Hejtmanek MR, Pollock JE. Chloroprocaine for spinal anesthesia: a retrospective analysis.
Acta anaesthesiologica Scandinavica 2011;55:267-72.
    3.   Yazicioglu D, Akkaya T, Kulacoglu H. Addition of lidocaine to bupivacaine for spinal
anaesthesia compared with bupivacaine spinal anaesthesia and local infiltration anaesthesia. Acta
anaesthesiologica Scandinavica 2013;57:1313-20.
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Is the purpose of this submission to obtain an exemption determination, in accordance with 45CFR46.101(b):  
No
  
Is the purpose of this submission to seek expedited review , as per the federal categories referenced in
45CFR46.110?
No
 
 
Is there any external funding or support that is applied for or awarded, or are you the recipient of a gift, for this
project?
No
 
 
 
 
Exempt and Expedited
Funding
Locations
Location Type
Facility Name
Domestic or
International
Geographic
Location
Local IRB Ethics
Approval
Local Site
Approval
Columbia/CUMC
MSCHONY 10
Personnel
UNI/Phone
Name
Role
Department
Edit/View
Obtaining
Informed Consent
rms7
212-305-5006
Smiley, Richard
Principal
Investigator
ANE Clinical
Operations
(751030X)
Edit
Y
Roles and Experience:  Chief Division of Obstetric Anesthesia
al3196
305-582-6077
Lee, Allison
Investigator
ANE Clinical
Operations
(751030X)
Edit
Y
Roles and Experience:  Co-investigator
bd2369
631-745-0180
Daoud, Bahaa
Investigator
ANE Education
(751040X)
Edit
Y
Roles and Experience:  Obstetric Anesthesia Fellow
br2469
212-305-3917
Raposo Corradini,
Beatriz
Investigator
ANE Research
Operations
(751050X)
View
Y
Roles and Experience:  Research coordinator
krb2115
917-575-5153
Bernstein, Kyra
Investigator
ANE Education
(751040X)
Edit
Y
Roles and Experience:  Obstetric Anesthesia Fellow
rl262
212-342-2028
Landau-Cahana,
Ruth
Investigator
ANE Clinical
Operations
(751030X)
View
Y
Roles and Experience:  Co-investigator
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Indicate the methods by which data/research records will be maintained or stored (select all that apply):
[x]Hardcopy (i.e., paper)
Describe where and how the data will be stored:
During the study period, any hard copy data collection materials will be stored in a secure cupboard in a locked
office on the CHONY Tower 10th floor, Room #1048. Following this period, once patient assessments have
concluded, the cover sheet of the data collection instrument, indicating the patient name and ID number will be
safely discarded and only de-identified hard copy (i.e, paper) data will be saved. No sensitive data will be saved.
Only de-identified data which does not contain sensitive information will be entered into a secure, encrypted web
site, RedCap, supported by CUMC.
[x]Electronic
Where will the data be stored?
Training and COI
The PI must ensure that each individual that is added as personnel has met the training requirements for this
study (http://www.cumc.columbia.edu/dept/irb/education/index.html). For help identifying which research
compliance trainings you may be required to take, visit the Research Compliance Training Finder.
UNI
Name
COI
HIPAA
HSP
(CITI)
Resear
ch with
Minors
(CITI)
FDA-
Regulat
ed
Resear
ch
(CITI)
S-I
CRC
Good
Clinical
Practic
e (GCP)
GCP -
Third-
party
trackin
g
GCP
Refresh
er
Genetic
Resear
ch
Consen
t
rms7
Smiley,
Richard
03/12/2
019
11/18/2
003
07/27/2
019
09/25/2
016
09/25/2
016
10/24/2
019
al3196
Lee,
Allison
02/25/2
019
10/08/2
012
06/02/2
018
06/02/2
018
06/02/2
018
bd2369
Daoud,
Bahaa
03/30/2
019
04/05/2
018
04/06/2
018
08/20/2
019
04/05/2
018
br2469
Raposo
Corradi
ni,
Beatriz
09/23/2
019
12/09/2
014
12/12/2
017
12/23/2
014
12/23/2
014
12/11/2
014
12/12/2
017
krb2115 Bernstei
n, Kyra
10/24/2
019
06/13/2
011
04/15/2
019
08/20/2
019
04/17/2
019
rl262
Landau-
Cahana
, Ruth
09/26/2
019
09/26/2
014
10/27/2
017
10/27/2
014
10/27/2
014
03/29/2
018
Departmental Approvers
Electronic Signature:  Bahaa Daoud (751040X) -
Investigator
Date:  10/16/2019
Electronic Signature:  Richard Smiley (751030X) - Principal
Investigator
Date:  10/11/2019
Electronic Signature:  Frances Antonetty (751050X) -
Department Administrator
Date:  10/14/2019
Electronic Signature:  Kyra Bernstein (751040X) -
Investigator
Date:  10/15/2019
Privacy & Data Security
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Y
[x]On a System
[  ]On an Endpoint 
Does this study involve the receipt or collection of Sensitive Data?
Yes
If any Sensitive Data is lost or stolen as part of your research protocol, you must inform both the IRB and the
appropriate IT Security Office (CUMC IT Security if at CUMC; CUIT if at any other University campus).
 
What type of Sensitive Data will be obtained or collected? Select all that apply:
[  ]Personally Identifiable Information (PII), including Social Security Numbers (SSN)
Will Social Security Numbers (SSNs) be collected for any purpose?
[x]Protected Health Information (PHI), including a Limited Data Set (LDS) 
If any PHI is lost or stolen, you must inform both the IRB and the Office of HIPAA Compliance.
 
 
Indicate plans for secure storage of electronic sensitive data: check all that apply
[x]Sensitive data will not be stored in electronic format
[  ]Sensitive data will be stored on a multi-user system
[  ]Sensitive data will be stored on an encrypted endpoint
Provide a description of how the confidentiality of study data will be ensured, addressing concerns or
protections that specifically relate to the data storage elements identified above (e.g. hard copy, electronic,
system, and/or endpoint):
During the study period of approximately 24 hours, any data collection materials will be stored in a secure cupboard in a
locked office on the CHONY Tower 10th floor, Room #1048. Following this period, once patient assessments have
concluded, the cover sheet of the data collection instrument, indicating the patient name and ID number will be safely
discarded and only de-identified data will be saved and discussed with investigators at this and other sites.
No sensitive data or PHI will be stored or shared electronically. De-indentified data will be stored using the CUMC
supported database system, RedCap, the data for which is stored on secure, encrypted servers.
 
The following individuals and/or agencies will be able to look at and copy research records:
The investigator, study staff and other medical professionals who may be evaluating the study; -Authorities from Columbia
University and New
York-Presbyterian Hospital, including the Institutional Review Board ('IRB’); -External, exclusive contractors who may be
reviewing compliance with research policies; -The Office of Human Research Protections ('OHRP')
 
If your project is not NIH funded, has a Certificate of Confidentiality (CoC) been requested for this research?
No
Provide a description of the protections in place to safeguard participants' privacy while information is being
collected:
During the study period of approximately 24 hours, any data collection materials will be stored in a secure cupboard in a
locked office on the CHONY Tower 10th floor, Room #1048. 
 
Procedures
IRB-AAAQ0916
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Is this project a clinical trial?
Yes
Is this project a clinical trial that requires registration with www.clinicaltrials.gov?
Yes
Has this study been registered with www.clinicaltrials.gov?
No
Please note that this section should be updated when the registration number is received. At this time,
please indicate who will be responsible for registering the study:
NCT02862912
Is this project associated with, or an extension of, an existing Rascal protocol?
No
Do study procedures involve any of the following?
Analysis of existing data and/or prospective record review
No
Audio and/or video recording of research subjects
No
Behavioral Intervention?
No
Biological specimens (collection or use of)
No
Cancer-related research
No
Drugs or Biologics
Yes
Future use of data and/or specimens
No
Genetic research
No
Human embryos or human embryonic stem cells
No
Imaging procedures or radiation
No
Medical Devices
No
Surgical procedures that would not otherwise be conducted or are beyond standard of care
No
Will any of the following qualitative research methods be used?
Survey/interview/questionnaire
No
Systematic observation of public or group behavior
No
Program evaluation
No
Will any of the following tests or evaluations be used?
Cognitive testing
No
IRB-AAAQ0916
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Educational testing
No
Non-invasive physical measurements
Yes
Taste testing
Yes
Is there an external protocol that describes ALL procedures in this study?
No
Please describe ALL study procedures in detail.
NOTE: Be sure to detail all of the procedures above to which a "yes" response was selected. Also detail any
additional procedures that may or may not fall into the categories listed above.
 
This will be a prospective, randomized, double blind clinical trial. Subjects will be ASA I and II women 18 yrs with
singleton pregnancy in the 1st or 2nd trimester of pregnancy undergoing cervical cerclage with spinal anesthesia.
Maternal height will be between 150 – 180 cm and the body mass index (BMI) 40 kg/m2. A member of the
investigation team will approach patients to discuss the study and obtain written informed consent following the
preoperative assessment and consent for anesthesia care for cervical cerclage.
 
After enrollment, each patient will be randomly allocated to the chloroprocaine (CP) or bupivacaine group (BUP) by
opening an opaque envelope with the assignment (CP) or (BUP). The randomization table will be created with block
randomization in blocks of 10. The proportion for the treatment and placebo groups will be 1:1. The investigator
opening the envelope will prepare the drug and provide it in a sterile fashion for the investigator who will administer the
drug, without revealing the group allocation
 
Exclusion criteria will include any contraindication to neuraxial anesthesia, history of  neurologic disease, including
multiple sclerosis, spinal stenosis, central or peripheral neuropathies, pre-existing/chronic back pain, ester local
anesthetic allergy, PABA allergy, or history of atypical cholinesterase (CP is metabolized by cholinesterase).
 
While receiving co-hydration with lactated Ringer’s solution 500 ml, patients will undergo spinal anesthesia at the L3-4
or L4-5 interspace with a midline approach, using a 25 G Whitacre spinal needle. Patients will be in the sitting or lateral
decubitus position, depending on the discretion of attending anesthesiologist.
 
Patients allocated to group CP will receive:  3% 2-chloroprocaine 50 mg (NesacaineR , Fresenius Kabi USA, LLC.
Lake Zurich) (1.67 ml) and fentanyl 15 mcg (0.3 ml).
 
Patients in the BUP group will receive hyperbaric 0.75% bupivacaine 9 mg (1.2 ml), with fentanyl 15 g (0.3 ml), with
saline (0.5 ml) to bring the volume to ~ 2 ml)
 
 Immediately following intrathecal injection, the patient will be laid supine. The patient, the anesthesiologist performing
the injection and all persons making subsequent observations will be blinded to the group allocation.
 
Sensory level to pinprick will be performed q 2 min until a constant sensory level has been achieved for 2 consecutive
tests. Motor block will also be assessed q 2 min using the Bromage scale:
 
Bromage Scale
I = free movement of the legs and feet  = no block
II = able to flex knees, with free movement of feet = partial (33%) block
III = unable to flex knees, but with free movement of the feet = almost complete (66%) block
IRB-AAAQ0916
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IV = unable to move legs or feet = complete block (100%)
 
Once a T12 sensory level to pinprick has been achieved, and after spending at least 3 min in the supine position, the
patient’s legs will be placed in stirrups bilaterally (lithotomy position).  Success of the block will be considered to be
T12 or higher. Inability to reach T12 within 20 min of injection will be considered a block failure.
 
Patient subjective intraoperative pain scores will be assessed according to a verbal rating scale (VRS) from 0 – 10,
where 0 = no pain and 10 = worst imaginable pain, at surgery start (placement of the speculum) and at the time of
clamp of the cervix.
 
Intraoperative complaints of pain (VRS > 4) will be treated with fentanyl 50 mcg iv q 5 min x 2 doses, prn. The
anesthetic will be considered a failure (operation) for either failure to achieve T12 sensory level to pinprick, or failure to
achieve a pain score of VRS   2 intraoperatively, despite 2 doses of fentanyl 50 mcg iv.
 
Any additional need for supplemental analgesics or anxiolysis, including the need to convert to general anesthesia, will
be at the discretion of the anesthesia attending.
In case of failure (induction) or failure (operation), conversion to another anesthetic technique and choice of technique
will be at the discretion of the attending anesthesiologist.
 
 
Data recorded:
 
Times:
•End spinal injection (t -IT)
•Anesthesia ready (sensory level T12 or higher)  - (t -ready)
•Time surgery start  - placement of speculum (t-start)
•Time cervix clamped (t- Cx)
•Time surgery end (t-End)
•Time of resolution sensory blockade (t- sensory)
•Time of motor block resolution –using Bromage score (t- motor)
•Time of ambulation unassisted  (t-amb)
•Time able to void (t-urine)
 
Other data to be recorded will be NPO time, preoperative and intraoperative fluid administration, intraoperative
nausea/vomiting and pruritus (none, mild, moderate, severe). The BP will be measured q 1 min for the first 5 min and
then q 3 – 5 min. Use of vasopressors intraoperatively will be recorded. We will record the need for supplemental iv
analgesia, anxiolytics, local anesthesia injection by the obstetrician. Perioperative administration of NSAIDs, and
obstetric complications such as vaginal bleeding, uterine contractions, abdominal pain will be documented.
 
Postoperatively, the sensory level to pinprick and motor block will be assessed by an investigator in the PACU, at q
15-min intervals for the first hour and then q 30 min until discharge. Patients will be asked about subjective pain using
a VRS from 0 – 10, where 0 = no pain and 10 = worst imaginable pain. At one hour, symptoms of nausea and pruritus
will be rated as none, mild, moderate, or severe. Postoperative (PACU) administration of supplemental analgesics or
treatment for pruritus or nausea, will be recorded.
 
The next day, between 18 - 30 hours postoperatively, the patient will be telephoned for follow-up by an investigator
who is blinded to the patient’s group allocation. The patient will be asked to rate their satisfaction with the anesthetic
for the procedure (complete, adequate or inadequate), symptoms of TNS (pain or abnormal sensations including
IRB-AAAQ0916
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hypoesthesia or dysesthesias in the gluteal region, radiating to the lower extremities). The patient will be asked to rate
the severity of those symptoms using a VRS from 0 – 10, where 0 = no pain and 10 = worst imaginable pain. She will
similarly be asked about back pain, headache and her use of post-operative analgesics. Patients with significant
symptoms of TNS, headache or other complication will be asked to return to CUMC for evaluation and management. If
any concerns or complications occur at any point during the study period, unblinding will occur and the principal
investigator will be notified immediately.
 
 
The primary outcome will be the mean difference between groups in time between the end of spinal injection (t IT) to
time for no motor block (t motor), i.e.  tIT  - T motor. Secondary outcomes will include the time to ambulate and void
(CUMC discharge criteria), rating of intraoperative discomfort, side effects and incidence of TNS.
 
 
On the General Information page you have indicated that the protocol version associated with the use of this
drug/biologic is as follows: 1
 
Please note that a Protocol Version # is required for protocols using a drug or biologic, and you will not be
allowed to submit this protocol until the Protocol Version # field is complete. Please ensure that the Protocol
Version # is completely and accurately reported on the General Information page.
 
List each drug or biologic that will be administered as the object of the protocol or is being used because it is
relevant to the aims of the research protocol. This applies whether the drug/biologic is not yet FDA-approved
(i.e., is investigational), is FDA approved and used in accordance with its labeling, or is an approved product that
is being used in an investigational manner (i.e., off-label use is being studied).
 
Note that the questions apply only to drugs used in clinical investigations. Emergency use of a drug that is not
yet FDA-approved is not a clinical investigation, and a submission in Rascal may not be required. Please contact
the IRB for assistance if emergency use of a drug or biologic that is not yet FDA-approved is being considered:
(212) 305-5883.
 
Name:
Bupivacaine HCl 0.75% in Dextrose 8.25% Injection
Dose:
9 mg
Study phase:
Phase 4
Manufacturer Information
Route of administration:
Intrathecal
Is the drug/biologic FDA-approved and used in accordance with its labeling?
Yes
Drugs/Biologics
Name:
Hospira, Inc.
Address:
Lake Forest, IL 60045 USA
Contact information:
(224) 212-2000
IRB-AAAQ0916
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 ( Y5M0 )
Approved for use until: 11/12/2020


●
●
●
A n I N D/ B B-I N D i s n ot r e q uir e d. A c o p y of t h e p a c k a g e i n s ert m u st b e att a c h e d.
N a m e:
C hl or o pr o c ai n e
D o s e:
5 0 m g
St u d y p h a s e:
P h a s e 4
M a n uf a ct ur er I nf or m ati o n
R o ut e of a d mi ni str ati o n:
I ntr at h e c al
I s t h e dr u g/ bi ol o gi c F D A- a p pr o v e d a n d u s e d i n a c c or d a n c e wit h it s l a b eli n g ?
N o
S el e ct a c at e g or y:
F D A- a p pr o v e d b ut n ot u s e d i n a c c or d a n c e wit h t h e c urr e ntl y a p pr o v e d l a b eli n g
D o e s t h e U s e of t h e dr u g/ bi ol o gi c r e q uir e a n I n v e sti g ati o n al N e w Dr u g (I N D) or Bi ol o gi c al I N D ( B B-I N D)
a p pli c ati o n ?
N O – t hi s u s e i s e x e m pt.
Si n c e y o u h a v e i n di c at e d t h at t h e dr u g/ bi ol o gi c i s eit h er F D A a p pr o v e d b ut b ei n g u s e d o ut si d e of it s
a p pr o v e d i n di c ati o n, or n ot F D A- a p pr o v e d, a n I N D i s r e q uir e d u nl e s s t h e cli ni c al i n v e sti g ati o n m e et s
crit eri a t o b e e x e m pt fr o m t h e I N D r e q uir e m e nt s. Pl e a s e c h o o s e t h e r e g ul at or y c at e g or y f or e x e m pti o n fr o m
t h e I N D r e q uir e m e nt s t h at a p pli e s t o y o ur st u d y.
2 1 C F R 3 1 2. 2( b)( 1) crit eri a m et - T hi s i s a cli ni c al i n v e sti g ati o n of a dr u g pr o d u ct t h at i s l a wf ull y m ar k et e d i n t h e
U nit e d St at e s a n d all t h e f oll o wi n g a p pl y: (i) T h e i n v e sti g ati o n i s n ot i nt e n d e d t o b e r e p ort e d t o F D A a s a w ell-
c o ntr oll e d st u d y i n s u p p ort of a n e w i n di c ati o n f or u s e n or i nt e n d e d t o b e u s e d t o s u p p ort a n y ot h er si g nifi c a nt
c h a n g e i n t h e l a b eli n g f or t h e dr u g; (ii) If t h e dr u g t h at i s u n d er g oi n g i n v e sti g ati o n i s l a wf ull y m ar k et e d a s a
pr e s cri pti o n dr u g pr o d u ct, t h e i n v e sti g ati o n i s n ot i nt e n d e d t o s u p p ort a si g nifi c a nt c h a n g e i n t h e a d v erti si n g f or t h e
pr o d u ct; a n d (iii) T h e i n v e sti g ati o n d o e s n ot i n v ol v e a r o ut e of a d mi ni str ati o n or d o s a g e l e v el or u s e i n a p ati e nt
p o p ul ati o n or ot h er f a ct or t h at si g nifi c a ntl y i n cr e a s e s t h e ri s k s ( or d e cr e a s e s t h e a c c e pt a bilit y of t h e ri s k s)
a s s o ci at e d wit h t h e u s e of t h e dr u g pr o d u ct.
T hi s i s a cli ni c al i n v e sti g ati o n of a dr u g pr o d u ct t h at i s l a wf ull y m ar k et e d i n t h e U nit e d St at e s a n d all t h e
f oll o wi n g a p pl y:
T h e i n v e sti g ati o n i s n ot i nt e n d e d t o b e r e p ort e d t o F D A a s a w ell- c o ntr oll e d st u d y i n s u p p ort of a n e w i n di c ati o n
f or u s e n or i nt e n d e d t o b e u s e d t o s u p p ort a n y ot h er si g nifi c a nt c h a n g e i n t h e l a b eli n g f or t h e dr u g;
If t h e dr u g t h at i s u n d er g oi n g i n v e sti g ati o n i s l a wf ull y m ar k et e d a s a pr e s cri pti o n dr u g pr o d u ct, t h e i n v e sti g ati o n
i s n ot i nt e n d e d t o s u p p ort a si g nifi c a nt c h a n g e i n t h e a d v erti si n g f or t h e pr o d u ct;
T h e i n v e sti g ati o n d o e s n ot i n v ol v e a r o ut e of a d mi ni str ati o n or d o s a g e l e v el or u s e i n a p ati e nt p o p ul ati o n or
ot h er f a ct or t h at si g nifi c a ntl y i n cr e a s e s t h e ri s k s ( or d e cr e a s e s t h e a c c e pt a bilit y of t h e ri s k s) a s s o ci at e d wit h t h e
u s e of t h e dr u g pr o d u ct;
Will t h e dr u g/ bi ol o gi c b e di s p e n s e d b y t h e C U M C R e s e ar c h P h ar m a c y, w hi c h i s r e s p o n si bl e f or t h e st or a g e,
h a n dli n g, a c c o u nt a bilit y, a n d di s p e n si n g of i n v e sti g ati o n al dr u g s t o r e s e ar c h i n v e sti g at or s ?  C U M C R e s e ar c h
P h ar m a c y p oli c y: htt p s://r e s e ar c h p h ar m a c y. c u m c. c ol u m bi a. e d u/ p oli ci e s. ht ml
N a m e:
A P P Fr e s e ni u s K a bi, U S A L L C
A d dr e s s:
T hr e e C or p or at e Dri v e
L a k e Z uri c h, Illi n oi s 6 0 0 4 7
C o nt a ct i nf or m ati o n:
M ai n P h o n e ( 8 4 7) 5 5 0- 2 3 0 0
I R B- A A A Q 0 9 1 6
P a g e 1 4 of 2 5
 ( Y 5 M 0 )
A p pr o v e d f or u s e u ntil: 1 1/ 1 2/ 2 0 2 0


●
●
N o, t h e dr u g will n ot b e di s p e n s e d b y t h e R e s e ar c h P h ar m a c y
Pl e a s e e x pl ai n:
T hi s dr u g i s alr e a d y u s e d fr e q u e ntl y a n d s af el y f or e pi d ur al a n d s pi n al i nj e cti o n at C U M C a n d ar o u n d t h e w orl d,
d e s pit e t h e F D A l a b eli n g. It i s n ot n e c e s s ar y t h at it b e di s p e n s e d b y t h e R e s e ar c h P h ar m a c y a s t h e dr u g i s alr e a d y
i n u s e at C U M C a n d u s e d i n t h e s a m e m a n n er i n w hi c h it will b e a d mi ni st er e d d uri n g t hi s st u d y. F urt h er m or e, si n c e
t h e dr u g i s u n st a bl e t o li g ht, it  m u st b e dr a w n u p i m m e di at el y b ef or e a d mi ni str ati o n. It w o ul d a ct u all y b e l e s s s af e
f or t h e dr u g t o b e pr e p ar e d b y t h e R e s e ar c h P h ar m a c y a n d s u b s e q u e ntl y tr a n sf err e d t o i n v e sti g at or s. T h e m o st
a p pr o pri at e m et h o d of pr e p ar ati o n w o ul d b e dr a wi n g u p t h e dr u g i n a st eril e f a s hi o n b y t h e cli ni ci a n a ct u all y
p erf or mi n g s pi n al a n e st h e si a at t h e ti m e of t h e pr o c e d ur e.
N a m e:
F e nt a n yl
D o s e:
1 5 m c g
St u d y p h a s e:
P h a s e 4
M a n uf a ct ur er I nf or m ati o n
R o ut e of a d mi ni str ati o n:
I ntr at h e c al
I s t h e dr u g/ bi ol o gi c F D A- a p pr o v e d a n d u s e d i n a c c or d a n c e wit h it s l a b eli n g ?
N o
S el e ct a c at e g or y:
F D A- a p pr o v e d b ut n ot u s e d i n a c c or d a n c e wit h t h e c urr e ntl y a p pr o v e d l a b eli n g
D o e s t h e U s e of t h e dr u g/ bi ol o gi c r e q uir e a n I n v e sti g ati o n al N e w Dr u g (I N D) or Bi ol o gi c al I N D ( B B-I N D)
a p pli c ati o n ?
N O – t hi s u s e i s e x e m pt.
Si n c e y o u h a v e i n di c at e d t h at t h e dr u g/ bi ol o gi c i s eit h er F D A a p pr o v e d b ut b ei n g u s e d o ut si d e of it s
a p pr o v e d i n di c ati o n, or n ot F D A- a p pr o v e d, a n I N D i s r e q uir e d u nl e s s t h e cli ni c al i n v e sti g ati o n m e et s
crit eri a t o b e e x e m pt fr o m t h e I N D r e q uir e m e nt s. Pl e a s e c h o o s e t h e r e g ul at or y c at e g or y f or e x e m pti o n fr o m
t h e I N D r e q uir e m e nt s t h at a p pli e s t o y o ur st u d y.
2 1 C F R 3 1 2. 2( b)( 1) crit eri a m et - T hi s i s a cli ni c al i n v e sti g ati o n of a dr u g pr o d u ct t h at i s l a wf ull y m ar k et e d i n t h e
U nit e d St at e s a n d all t h e f oll o wi n g a p pl y: (i) T h e i n v e sti g ati o n i s n ot i nt e n d e d t o b e r e p ort e d t o F D A a s a w ell-
c o ntr oll e d st u d y i n s u p p ort of a n e w i n di c ati o n f or u s e n or i nt e n d e d t o b e u s e d t o s u p p ort a n y ot h er si g nifi c a nt
c h a n g e i n t h e l a b eli n g f or t h e dr u g; (ii) If t h e dr u g t h at i s u n d er g oi n g i n v e sti g ati o n i s l a wf ull y m ar k et e d a s a
pr e s cri pti o n dr u g pr o d u ct, t h e i n v e sti g ati o n i s n ot i nt e n d e d t o s u p p ort a si g nifi c a nt c h a n g e i n t h e a d v erti si n g f or t h e
pr o d u ct; a n d (iii) T h e i n v e sti g ati o n d o e s n ot i n v ol v e a r o ut e of a d mi ni str ati o n or d o s a g e l e v el or u s e i n a p ati e nt
p o p ul ati o n or ot h er f a ct or t h at si g nifi c a ntl y i n cr e a s e s t h e ri s k s ( or d e cr e a s e s t h e a c c e pt a bilit y of t h e ri s k s)
a s s o ci at e d wit h t h e u s e of t h e dr u g pr o d u ct.
T hi s i s a cli ni c al i n v e sti g ati o n of a dr u g pr o d u ct t h at i s l a wf ull y m ar k et e d i n t h e U nit e d St at e s a n d all t h e
f oll o wi n g a p pl y:
T h e i n v e sti g ati o n i s n ot i nt e n d e d t o b e r e p ort e d t o F D A a s a w ell- c o ntr oll e d st u d y i n s u p p ort of a n e w i n di c ati o n
f or u s e n or i nt e n d e d t o b e u s e d t o s u p p ort a n y ot h er si g nifi c a nt c h a n g e i n t h e l a b eli n g f or t h e dr u g;
If t h e dr u g t h at i s u n d er g oi n g i n v e sti g ati o n i s l a wf ull y m ar k et e d a s a pr e s cri pti o n dr u g pr o d u ct, t h e i n v e sti g ati o n
N a m e:
H o s pir a, I n c,
A d dr e s s:
2 7 5 N Fi el d Dr, L a k e F or e st, I L 6 0 0 4 5
C o nt a ct i nf or m ati o n:
( 2 2 4) 2 1 2- 2 0 0 0
I R B- A A A Q 0 9 1 6
P a g e 1 5 of 2 5
 ( Y 5 M 0 )
A p pr o v e d f or u s e u ntil: 1 1/ 1 2/ 2 0 2 0


●
i s n ot i nt e n d e d t o s u p p ort a si g nifi c a nt c h a n g e i n t h e a d v erti si n g f or t h e pr o d u ct;
T h e i n v e sti g ati o n d o e s n ot i n v ol v e a r o ut e of a d mi ni str ati o n or d o s a g e l e v el or u s e i n a p ati e nt p o p ul ati o n or
ot h er f a ct or t h at si g nifi c a ntl y i n cr e a s e s t h e ri s k s ( or d e cr e a s e s t h e a c c e pt a bilit y of t h e ri s k s) a s s o ci at e d wit h t h e
u s e of t h e dr u g pr o d u ct;
Will t h e dr u g/ bi ol o gi c b e di s p e n s e d b y t h e C U M C R e s e ar c h P h ar m a c y, w hi c h i s r e s p o n si bl e f or t h e st or a g e,
h a n dli n g, a c c o u nt a bilit y, a n d di s p e n si n g of i n v e sti g ati o n al dr u g s t o r e s e ar c h i n v e sti g at or s ?  C U M C R e s e ar c h
P h ar m a c y p oli c y: htt p s://r e s e ar c h p h ar m a c y. c u m c. c ol u m bi a. e d u/ p oli ci e s. ht ml
N o, t h e dr u g will n ot b e di s p e n s e d b y t h e R e s e ar c h P h ar m a c y
Pl e a s e e x pl ai n:
F e nt a n yl i s n ot e x pli citl y F D A- a p pr o v e d f or i ntr at h e c al u s e b ut i s e xtr e m el y wi d el y u s e d f or t hi s p ur p o s e w orl d wi d e
a n d at C U M C. T h er e i s a n e xt e n si v e b o d y of lit er at ur e s u p p orti n g t h e u s e of f e nt a n yl i ntr at h e c all y i n o b st etri c
p ati e nt s. F e nt a n yl i s alr e a d y r o uti n el y a d mi ni st er e d d uri n g s pi n al a n e st h e si a f or c er vi c al c er cl a g e at C U M C - it i s
n ot b ei n g u s e d a s a n i n v e sti g ati o n al dr u g, it i s n ot b ei n g st u di e d i n t hi s tri al a n d d o e s n ot n e e d t o b e di s p e n s e d b y
t h e R e s e ar c h P h ar m a c y. Pr e p ar ati o n b y t h e R e s e ar c h P h ar m a c y a n d t h e n tr a n sf er t o i n v e sti g at or s w o ul d b e l e s s
s af e t h a n t h e m a n n er i n w hi c h t h e dr u g i s alr e a d y r o uti n el y pr e p ar e d. T h e s af e st a n d m o st a p pr o pri at e  m et h o d of
pr e p ar ati o n will b e t h e cli ni ci a n dr a wi n g u p t h e dr u g i n a st eril e f a s hi o n i m m e di at el y b ef or e a d mi ni str ati o n i n t h e
o p er ati n g r o o m, a s i s c urr e ntl y o ur r o uti n e pr a cti c e. A d di n g a s e p ar at e pr o c e d ur e wit h di s p e n si n g of t h e dr u g b y t h e
R e s e ar c h P h ar m a c y f or a dr u g t h at i s alr e a d y r o uti n el y pr e p ar e d a n d a d mi ni st er e d b y  cli ni ci a n s c o ul d ri s k a d di n g
c o nf u si o n t o t h e pr o c e s s a n d d e cr e a s e s af et y of a d mi ni str ati o n.
 
 
R e cr uit m e nt:
 
Will y o u o bt ai n i nf or m ati o n or bi o s p e ci m e n s f or p ur p o s e s of s cr e e ni n g or d et er mi ni n g eli gi bilit y ?
N o
 
D e s cri b e h o w p arti ci p a nt s will b e r e cr uit e d:
A m e m b er of t h e i n v e sti g ati o n t e a m will a p pr o a c h p ati e nt s t o di s c u s s t h e st u d y a n d o bt ai n writt e n i nf or m e d c o n s e nt
f oll o wi n g t h e pr e o p er ati v e a s s e s s m e nt a n d c o n s e nt f or a n e st h e si a c ar e f or c er vi c al c er cl a g e.
 
S el e ct all m et h o d s b y w hi c h p arti ci p a nt s will b e r e cr uit e d:
[  ]  St u d y d o e s n ot i n v ol v e r e cr uit m e nt pr o c e d ur e s
[ x]  P er s o n t o P er s o n
[  ]  R a di o
[  ]  N e w s p a p er s
[  ]  Dir e ct M ail
[  ]  W e b sit e
[  ]  E m ail
[  ]  T el e vi si o n
[  ]  T el e p h o n e
[  ]  Fl y er/ H a n d o ut
[  ]  N e w sl ett er/ M a g a zi n e/ J o ur n al 
[  ]  R e s e ar c h M at c h
[  ]  C U M C R e cr uit M e
 
R e cr uit m e nt A n d C o n s e nt
I R B- A A A Q 0 9 1 6
P a g e 1 6 of 2 5
 ( Y 5 M 0 )
A p pr o v e d f or u s e u ntil: 1 1/ 1 2/ 2 0 2 0


Additional Study Information: Please add a description of your study as you would like it to be
displayed on the RecruitMe website.
  
Informed Consent Process:
 
Informed Consent Process, Waiver or Exemption: Select all that apply
 
[x]  Informed consent with written documentation will be obtained from the research participant or appropriate
representative.
 
Documentation of informed consent is applicable to:
The study in its entirety
 
Identify the portion of the study (e.g., prospective portion, focus groups, substudy 2) or
subject population for which documentation of consent will be obtained::
 
Documentation of participation will be obtained from::
[x]  Adult participants
[  ]  Parent/Guardian providing permission for a child's involvement
[  ]  Legally Authorized Representatives (LARs)
 
Describe how participants' written consent will be obtained:
A member of the investigation team who will be involved in the care of the patient will approach patients
to discuss the study and obtain written informed consent following the preoperative assessment and
consent for anesthesia care for cervical cerclage. A thorough explanation of the protocol will be given by
the investigator. Same day consent is requested. Subjects must be recruited on the same day of care,
since it is often not possible to know well in advance which patients will require cervical cerclage.
 
The consent process will include the IRB suggested language, including giving patients a clear
opportunity to decline. Obstetric patients are frequently accompanied by family members and close
friends, and their presence and participation will be encouraged during the informed consent discussion,
unless of course the patient does not want such participation. Subjects will be given sufficient time to
make a decision and will not be approached after administration of medications that may alter the
cognitive state. We will document in the screening log, the time of start of the consent process and the
time that consent was obtained.
 
[  ]  Informed consent will be obtained but a waiver of written documentation of consent (i.e., agreement to
participate in the research without a signature on a consent document) is requested.
 
[  ]  A waiver of some or all elements of informed consent (45 CFR 46.116) is requested.
 
[  ]  Planned Emergency Research with an exception from informed consent as per 21 CFR 50.24.
 
[  ]  This is exempt research.
  
Subject Language
Enrollment of non-English speaking subjects is expected.
IRB-AAAQ0916
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Languages anticipated:
Spanish
 
As you plan on enrolling non-English speaking subjects, administrative IRB approval of the
translated documents (e.g., consent, recruitment materials, questionnaires) in the above selected
languages are required. Please see the IRB's policy on the Enrollment of Non-English Speaking
Subjects in Research for further details
 
(http://www.cumc.columbia.edu/dept/irb/policies/documents/Nonenglishspeakingsubjects.Revised.F
INALDRAFT.111909.website.doc).
  
Capacity to Provide Consent: 
 
Do you anticipate using surrogate consent or is research being done in a population where capacity to
consent may be questionable? 
No
 
 
Research Question(s)/Hypothesis(es):
Our hypothesis is that the use of chloroprocaine for outpatient spinal anesthesia for cervical
cerclage will lead to faster recovery of motor and sensory function than bupivacaine spinal
anesthesia, which is currently the customary practice at CUMC. We believe CP spinal anesthesia,
compared with the bupivacaine spinal anesthesia, will result in higher patient and higher staff
satisfaction, and potentially economic benefits associated with earlier PACU discharge and
decreased nursing staff workload. The primary outcome will be the mean difference between
groups in time between the end of spinal injection (t IT) to time for no motor block (t motor), i.e. 
tIT  - T motor. Secondary outcomes will include the time to ambulate and void (CUMC discharge
criteria), rating of intraoperative discomfort, side effects and incidence of TNS. 
  
Scientific Abstract:
Cervical insufficiency, defined as the inability of the uterine cervix to retain a pregnancy in the
second trimester, in the absence of uterine contractions,1 affects 1% of the obstetric population
(about 1 in 500 pregnancies)2 and 8% of populations with recurrent miscarriages and mid-trimester
pregnancy losses.3 Cervical cerclage is a surgical procedure performed via the vaginal route,
whereby a suture is inserted at the junction of vagina and cervix, at the level of the internal os of
the cervix, to provide mechanical support and prevent preterm birth. The procedure is usually
performed as an elective outpatient procedure with a duration of approximately 30 minutes, but
occasionally is performed as an emergency, in the case of threatened miscarriage. An anesthetic
technique with a relatively short duration of action and recovery is indicated. Both regional and
general anesthesia have been successfully used,2 however spinal anesthesia is now
overwhelmingly the choice, as it has the advantage of preserving maternal airway reflexes and
limiting fetal exposure to anesthetic agents (although the procedure is usually performed beyond
the stage of highest teratogenicity risk). Throughout most of the 1990s, lidocaine was the
Research Aims & Abstracts
IRB-AAAQ0916
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intrathecal local anesthetic agent of choice for these procedures, but fell out of favor because of
the frequency of reports of transient neurologic symptoms (TNS)- the reported incidence ranges
from 10 – 40%.4-6 Patients with TNS experience cramping, aching, or lancinating pain affecting the
lower extremities and buttocks. Symptoms, which may have variable severity, occur within 6 - 36
hours after spinal anesthesia and last between 1 – 7 days. Bupivacaine is now the most common
local anesthetic used for this procedure. Bupivacaine is associated with far less TNS but is a long-
acting agent and carries the disadvantage of a prolonged anesthetic recovery, which is a source of
significant patient dissatisfaction and impacts staffing and resources due to unnecessarily long
post-anesthesia care unit (PACU) stays. In our practice at CUMC, with typical dosing of intrathecal
hyperbaric bupivacaine 0.75% ranging from 7.5 – 9 mg, usually in conjunction with fentanyl 10 –
20 mcg, patients sometimes spend 5 hours or more in the PACU after a 30-minute outpatient
cervical cerclage procedure. These prolonged stays are partly a consequence of the CUMC
practice that maintains that patients must be able to void and ambulate independently prior to
discharge home, due to concerns about the risk of falls and readmission for urinary
retention. Chloroprocaine (2-chloroprocaine, CP) is an amino-ester local anesthetic with a fast
onset and short duration that has made a resurgence for use in spinal anesthesia for ambulatory
procedures.7 Although safe reports of its use for spinal anesthesia were published following its
introduction in 1952,8 CP was never widely adopted, probably due to the availability of lidocaine,
which had been introduced in 1949. The drug has had widespread use for epidural anesthesia,
and due to its rapid onset and low systemic toxicity, is considered to be critical for the safe practice
of obstetric anesthesiology (including at CUMC) for use in emergencies such as “stat” cesarean
sections in women with epidural catheters in place for labor anlagesia. Serious concerns about the
safety of the use of CP intrathecally arose in the wake of a series of case reports in the 1980’s of
catastrophic neurologic sequelae, such as adhesive arachnoiditis, following the injection of large
doses of the drug (average 611 mg) that had been meant to be injected into the epidural space.9-
11 Neurotoxicity was attributed to the preservative sodium bisulphite, which was hypothesized to
provoke the release of sulphur dioxide, in the presence of the low pH of CP. Animal studies have
been inconclusive, with conflicting results believed to be related to interspecies variation in levels
of sulfur oxidase (catalyzes sulfites to sulfates), although variable results have also been seen in
studies involving the same species.12 The current formulation of CP has no additives. Vaghadia et
al.13 performed a recent trial involving 40 patients randomized to undergo transurethral resection
of the prostate with spinal anesthesia with either preservative free CP or lidocaine. Several
patients in the lidocaine group experienced TNS, and notably one patient in the CP group
developed an incomplete cauda equina syndrome that developed 24 hours later and persisted for
several weeks. The cause of that unfortunate complication is unclear. Contemporary reports of use
spinal CP began to reappear in small studies in volunteers in the mid-2000’s and then larger
studies followed, investigating its properties, such as minimum effective dose, and behavior with
added dextrose and clonidine, as well as comparisons with bupivacaine and lidocaine.14-26 This
work supports the safety of the use of spinal CP, demonstrates the low incidence of TNS and
particular suitability for surgeries in an ambulatory practice setting. CP is currently used very
frequently at CUMC for spinal anesthesia for ambulatory surgical patients, especially for lower
extremity orthopedic procedures such as knee arthroscopy. A Departmental review of CUMC
practice between 2010 – 2013 reported 358 cases of in which CP has been used for spinal
anesthesia, with no associated complications noted. 27 To our knowledge there are no published
reports of the use of CP for spinal anesthesia for cervical cerclage or other outpatient procedures
IRB-AAAQ0916
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in obstetric population. We plan to perform an observational study in which patients undergoing
cervical cerclage under spinal anesthesia will be randomized to receive either plain 3% 2-
chloroprocaine 50 mg or hyperbaric bupivacaine 9mg in conjunction with 15 mcg fentanyl. Our
hypothesis is that the use of chloroprocaine for outpatient spinal anesthesia for cervical cerclage
will lead to faster recovery of motor and sensory function than bupivacaine spinal anesthesia,
which is currently the customary practice at CUMC. We believe CP spinal anesthesia, compared
with the bupivacaine spinal anesthesia, will result in higher patient and higher staff satisfaction,
and potentially economic benefits associated with earlier PACU discharge and decreased nursing
staff workload.    
  
Lay Abstract:
Cervical insufficiency, defined as the inability of the uterine cervix to retain a pregnancy in the
second trimester, in the absence of uterine contractions, affects 1% of pregnant women. Cervical
cerclage is a surgical procedure performed via the vaginal route, whereby a suture is inserted at
the junction of vagina and cervix, to provide mechanical support and prevent preterm birth. The
procedure is usually performed as an elective outpatient procedure with a duration of
approximately 30 minutes, but occasionally is performed as an emergency, in the case of
threatened miscarriage. Both regional and general anesthesia have been successfully used,
however spinal anesthesia is now overwhelmingly the choice, as it allows the mother to breather
on her own and limits the exposure of the fetus to anesthetic agents. Throughout most of the
1990s, lidocaine was the local anesthetic agent of choice for spinal anesthesia, but fell out of favor
because of the frequency of reports of transient neurologic symptoms (TNS). Patients with TNS
experience cramping, aching, or lancinating pain affecting the lower extremities and buttocks.
Bupivacaine is now the most common local anesthetic used for this procedure. Bupivacaine is
associated with far less TNS but is a long-acting agent and carries the disadvantage of a
prolonged anesthetic recovery, which is a source of significant patient dissatisfaction and impacts
staffing and resources due to unnecessarily long post-anesthesia care unit (PACU)
stays. Chloroprocaine (2-chloroprocaine, CP) is an amino-ester local anesthetic with a fast onset
and short duration that has made a resurgence for use in spinal anesthesia for ambulatory
procedures.  Serious concerns about the safety of the use of CP intrathecally arose in the wake of
a series of case reports in the 1980’s of catastrophic neurologic sequelae, such as adhesive
arachnoiditis, following the injection of large doses of the drug (average 611 mg) that had been
meant to be injected into the epidural space. Neurotoxicity was attributed to the preservative
sodium bisulphite. The current formulation of CP has no additives. Contemporary reports of use
spinal CP have been published since the mid-2000’s and then larger studies followed, investigating
its properties. This work supports the safety of the use of spinal CP, demonstrates the low
incidence of TNS and particular suitability for surgeries in an ambulatory practice setting. CP is
currently used very frequently at CUMC for spinal anesthesia for ambulatory surgical patients,
especially for lower extremity orthopedic procedures such as knee arthroscopy. A Departmental
review of CUMC practice between 2010 – 2013 reported 358 cases of in which CP has been used
for spinal anesthesia, with no associated complications noted. To our knowledge there are no
published reports of the use of CP for spinal anesthesia for cervical cerclage or other outpatient
procedures in obstetric population. We plan to perform an observational study in which patients
undergoing cervical cerclage under spinal anesthesia will be randomized to receive either plain 3%
2-chloroprocaine 50 mg or hyperbaric bupivacaine 9mg in conjunction with 15 mcg fentanyl. Our
IRB-AAAQ0916
Page 20 of 25
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hypothesis is that the use of chloroprocaine for outpatient spinal anesthesia for cervical cerclage
will lead to faster recovery of motor and sensory function than bupivacaine spinal anesthesia,
which is currently the customary practice at CUMC. We believe CP spinal anesthesia, compared
with the bupivacaine spinal anesthesia, will result in higher patient and higher staff satisfaction,
and potentially economic benefits associated with earlier PACU discharge and decreased nursing
staff workload.   
 
 
Abbreviated Submission:
The IRB has an abbreviated submission process for multicenter studies supported by industry or NIH
cooperative groups (e.g., ACTG, HVTN, NCI oncology group studies, etc.), and other studies that have a complete
stand-alone protocol. The process requires completion of all Rascal fields that provide information regarding
local implementation of the study. However, entering study information into all of the relevant Rascal fields is not
required, as the Columbia IRBs will rely on the attached stand-alone (e.g., sponsor's) protocol for review of the
overall objectives. .
If you select the Abbreviated Submission checkbox and a section is not covered by the attached stand-alone
protocol, you will need to go back and provide this information in your submission. 
  
Potential Risks:
Provide information regarding all risks to participants that are directly related to participation in this protocol,
including any potential for a breach of confidentiality. Risks associated with any of the items described in the
Procedures section of this submission should be outlined here if they are not captured in a stand-alone protocol.
Risks of procedures that individuals would be exposed to regardless of whether they choose to participate in this
research need not be detailed in this section, unless evaluation of those risks is the focus of this research. When
applicable, the likelihood of certain risks should be explained and data on risks that have been encountered in
past studies should be provided.
[  ]  Abbreviated Submission - This information is included in an attached stand-alone protocol. Proceed to the next
question
 Spinal anesthesia is routinely performed for cervical cerclage at CUMC. Spinal anesthesia with
either relatively low dose bupivacaine or choroprocaine is considered to be safe and does not
present significant additional risk to receiving routine spinal anesthesia care at CUMC.
  
Potential Benefits:
Provide information regarding any anticipated benefits of participating in this research. There should be a
rational description of why such benefits are expected based on current knowledge. If there is unlikely to be
direct benefit to participants/subjects, describe benefits to society. Please note that elements of participation
such as compensation, access to medical care, receiving study results, etc. are not considered benefits of
research participation.
[  ]  Abbreviated Submission - This information is included in an attached stand-alone protocol. Proceed to the next
question
 Patients in the chloroprocaine group may benefit from earlier resolution of motor and sensory
block and earlier discharge from the post-anesthesia care unit. 
  
Alternatives:
Risks, Benefits & Monitoring
IRB-AAAQ0916
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If this research involves an intervention that presents greater than minimal risk to participants, describe available
alternative interventions and provide data to support their efficacy and/or availability. Note, participants always
have the option not to participate in research.
[  ]  Abbreviated Submission - This information is included in an attached stand-alone protocol. Proceed to the next
question
 Alternatives to not participating in the study are to receive spinal anesthesia with a local anesthetic
agent chosen by the anesthesiology attending. 
  
Data and Safety Monitoring:
Describe how data and safety will be monitored locally and, if this is a multi-center study, how data and safety
will be monitored across sites as well.
[  ]  Abbreviated Submission - This information is included in an attached stand-alone protocol. Proceed to the next
question
 During the study period of approximately 24 hours, any data collection materials will be stored in a
secure cupboard in a locked office on the CHONY Tower 10th floor, Room #1048. Following this
period, once patient assessments have concluded, the cover sheet of the data collection
instrument, indicating the patient name and ID number will be safely discarded and only de-
identified data will be saved and discussed with investigators at this and other sites.No sensitive
data or PHI will be stored or shared electronically. De-indentified data will be stored using the
CUMC supported database system, RedCap, the data for which is stored on secure, encrypted
servers.The principal investigator will be responsible for data and safety monitoring. The principal
investigator,  in conjunction with co-investigators will monitor closely for any issues, concerns or
complications during follow-up of the patients. Patients will also be provided with the contact
information of the principal investigator in order to report any unanticipated problems. Any
unanticipated problems (i.e., events, outcomes, or occurrences that are unexpected, at least
possibly related to the research, and suggest an increase in risk of harm to subjects or others) that
arise will be reported to the IRB as soon as possible- by 1 week at the very latest.A data safety
monitoring board has not been established for this project. Any  adverse events will be immediately
reported to the principal investigator. The principal investigator will also perform a biannual review
of the data collected in order to identify unexpected issues. 
 
 
Unless otherwise noted, the information entered in this section should reflect the  number of subjects enrolled or
accrued under the purview of Columbia researchers, whether at Columbia or elsewhere.
Target enrollment:
50
Number enrolled to date:
43
Number enrolled since the last renewal or, if this is the first renewal, since the initial approval:
20
Number anticipated to be enrolled in the next approval period:
7
Does this study involve screening/assessment procedures to determine subject eligibility?
Yes
Subjects
IRB-AAAQ0916
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Target accrual:
50
Number accrued to date:
43
Number accrued since the last renewal or, if this is the first renewal, since the initial approval:
20
Number anticipated to be accrued in the next approval period:
7
Of the number of subjects enrolled, or the number accrued for interventional studies with a screening process:
How many remain on the study?
0
How many are off study?
44
How many completed the study?
43
Have any withdrawn of their own initiative?
No
Have any been removed by PI?
Yes
How many?
1
Please explain:
Unable to perform/complete study due to other issues to manage on the labor floor so patient had her cerclage
anesthesia according to usual clinical care
Have any been lost to follow-up?
No
Have any died while on study?
No
Have any subject complaints been received?
No
Is this a multi-center study?
No
Does this study have one or more components that apply to a subset of the overall study population (e.g. Phase
1/2, sub-studies)?
No
Of the number enrolled, or the number accrued for interventional studies with a screening process, indicate:
Population Gender
Population Age
Population Race
Females
Males
Non Specific
100%
0%
0%
0-7
8-17
18-65
>65
Non Specific
0%
0%
100%
0%
0%
IRB-AAAQ0916
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Population Ethnicity
Vulnerable Populations as per 45 CFR 46:
Will children/minors be enrolled
No
Will pregnant women/fetuses/neonates be targeted for enrollment?
Yes
What is the level of risk to the pregnant woman?
Minimal Risk
What is the level of risk to the fetus?
Minimal Risk
What is the level of risk to the neonate?
Minimal Risk
Indicate all groups for which there is a prospect of direct benefit:
[x]Pregnant women
[  ]Fetuses
[  ]Neonates
[  ]No prospect of direct benefit
Will prisoners be targeted for enrollment?
No
Other Vulnerable Populations:
[  ]Individuals lacking capacity to provide consent
[  ]CU/NYPH Employees/Residents/Fellows/Interns/Students
[  ]Economically disadvantaged
[  ]Educationally disadvantaged
[x]Non-English speaking
Please ensure that your plan to enroll subjects in their primary language is described on the Informed
Consent page.
[  ]Other Vulnerable populations
[  ]None of the Populations listed above will be targeted for Enrollment
Subject Population Justification:
This study will be carried out in pregnant women undergoing cervical cerclage so necessitates a subject population that is
exclusively pregnant women.
Does this study involve compensation or reimbursement to subjects?
No
 
 
American
Indian/Alaskan
Native
Asian
Native Hawaiian
or Other Pacific
Islander
Black or African
American
White
More than One
Race
Non-Specific
0%
0%
0%
0%
0%
0%
100%
Hispanic or Latino
Not Hispanic or Latino
Non-Specific
0%
0%
100%
Attached HIPAA Forms
IRB-AAAQ0916
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Number
Type
Title
Status
AAAM9053
A
Chloroprocaine spinal
anesthesia for cervical
cerclage
Approve
Attached Consent Forms
Number
Copied From
Form Type
Title
Active/InActive
Initiator
AAAT6471
AAAT6471
Consent
Chloroprocaine spinal
anesthesia for cerclage
Active
Richard Smiley (rms7)
Documents
Archived
Document
Identifier
Document Type
File Name
Active
Stamped
Date Attached
Created By
No
Revised Consent
Tracked Changes
Consent
Form/Addendum
AAAQ0906_ICF_
IRBTrackedChan
ges Lee
2_8_16.docx
Y
02/08/2016
Allison Lee
(al3196)
No
AAAQ0906_ICF_
IRBTrackedChan
ges
Consent
Form/Addendum
AAAQ0906_ICF_
IRBTrackedChan
ges.docx
N
01/28/2016
Diana Lesmes
(dl3041)
No
Bupivacaine
package insert
Investigator
Brochure/Packag
e Insert/Device
Manual
Bupivacaine
package insert
Hospira.pdf
Y
10/07/2015
Allison Lee
(al3196)
No
Chloroprocaine
package insert
Investigator
Brochure/Packag
e Insert/Device
Manual
Chloroprocaine
package
insert.pdf
Y
08/03/2015
Allison Lee
(al3196)
No
Data Collection
Sheet CP vs.
Bupi PDF
Other
Data Collection
Sheet CP vs.
Bupi PDF.pdf
Y
01/27/2016
Yaritza Collazo
(yr111)
No
Data collectio
sheet 08/2017
Other
Data Collection
Sheet CP vs.
Bupi
Revised_2017.pd
f
Y
Y
08/18/2017
Richard Smiley
(rms7)
No
Fentanyl Pkg
Insert
Other
Fentanyl Pkg
Insert.pdf
Y
01/27/2016
Yaritza Collazo
(yr111)
No
Telephone Script
Other
Telephone
Script.pdf
Y
01/27/2016
Yaritza Collazo
(yr111)
No
Data Collection
Sheet
Study
Material/Instrume
nt
Data Collection
Sheet CP vs.
Bupi PDF.pdf
Y
Y
10/07/2015
Allison Lee
(al3196)
IRB-AAAQ0916
Page 25 of 25
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ICF_000.pdf: 
Columbia University Medical Center Consent Form
Attached to Protocol:  IRB-AAAQ0916
Principal Investigator: Richard Smiley (rms7)
IRB Protocol Title:  
Chloroprocaine versus bupivacaine spinal anesthesia for cervical 
cerclage
Consent Number: 
CF-AAAT6471
Participation Duration: 
12 hours
Anticipated Number of Subjects: 
60
Contact
Contact
Contact
Title
Title
Contact Type
Contact Type
Numbers
Numbers
Richard Smiley
Richard Smiley
Virginia Apgar MD 
Professor of 
Anesthesiology
Virginia Apgar MD 
Professor of 
Anesthesiology
Principal 
Investigator
Principal 
Investigator
Telephone:  212-305-5006
Telephone:  212-305-5006
Pager:         9178992560
Pager:         9178992560
Cell:           9145849531
Cell:           9145849531
Research Purpose
You are invited to participate in a research study which is designed to determine whether or not spinal 
anesthesia with the local anesthetic drug, chloroprocaine,  wears off faster than the local anesthetic 
drug, bupivacaine, and results in faster discharge from the post-anesthesia care unit after surgery.
Background:
You are scheduled to undergo cervical cerclage with spinal anesthesia. Over 90% of these procedures 
at CUMC are performed with spinal anesthesia because this allows the woman to be awake, to 
breathe on her own, and limits the amount of medication that crosses to the fetus. Because the 
procedure usually lasts approximately 30 minutes, an anesthetic technique with a relatively short 
duration of action and recovery is indicated. Bupivacaine is now the most common local anesthetic 
used for this procedure. Bupivacaine is safe and has been preferred over other medications such as 
lidocaine, because it is associated with a low incidence of a complication from spinal anesthesia 
known as “transient neurologic symptoms” – a condition where pain and cramping in the b uttocks 
and lower extremities can be experienced for several days. Bupivacaine is a long-acting local 
anesthetic agent and therefore has the disadvantage of a prolonged anesthetic recovery that may last a 
few hours. 
Chloroprocaine is a local anesthetic with a fast onset and short duration that may be used for spinal 
anesthesia for ambulatory procedures. Chloroprocaine is currently used at CUMC for spinal 
anesthesia for ambulatory surgical patients, especially for lower extremity orthopedic procedures such 
as knee arthroscopy. It is also used at CUMC for pregnant patients like yourself. 
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In our study, patients undergoing cervical cerclage under spinal anesthesia will be randomized, by a 
process similar to ﬂipping a coin, to receive either chloroprocaine or bupivacaine for their spinal 
anesthesia. We will observe and compare how fast the anesthesia sets in, how comfortable you are 
during your surgery, how long it takes to wear off and how long it takes to be discharged from the 
Post-Anesthesia Care Unit. We will call you the next day to check if you are having any complaints or 
concerns related to the spinal anesthesia you received.
Information on Research
We are doing this research study to compare the onset, action and duration of the local anesthetic 
medications chlorprocaine and bupivacaine for spinal anesthesia. You are being asked to take part in 
this study because you are undergoing cervical cerclage with spinal anesthesia. About 50 people are 
expected to be enrolled in this study at CUMC. Off label use of an approved drug chloroprocaine is 
being used in an investigational manner (not for the purpose that it is approved for) in this research 
study. This means that chloroprocaine has been approved by the Food and Drug Administration 
(FDA) for use in nerve blocks, but it has not been approved for epidural or spinal anesthesia. You 
should understand that although chlororprocaine is not approved by the FDA for use in this manner, at 
CUMC and many hospitals around the US, we have a lot of experience using chloroprocaine quite 
safely for both epidural and spinal anesthesia. In fact the use of chloroprocaine at CUMC between 
2010 and 2013 was studied by members of our Department and it was reported that out of 358 cases 
in which chloroprocaine was used for spinal anesthesia, there were no complications noted. Because 
of the safety, low toxicity and fast onset of chloroprocaine, it is also the drug we use most commonly 
for epidural anesthesia for emergency surgeries in pregnant women at CUMC.
Risks
Spinal anesthesia with either relatively low dose bupivacaine or choroprocaine is considered to be 
safe and does not present signiﬁcant additional risk to receiving routine spinal anesthesia care at 
CUMC.  Both medications are currently used at CUMC for anesthesia for cerclage. To the best of our 
knowledge, taking part in this study will not hurt you.
Beneﬁts
You may or may not receive personal (direct) beneﬁt from taking part in this study. The possible 
beneﬁts of taking part in this study is that patients in the chloroprocaine group may have earlier 
resolution of the anesthesia block and have earlier discharge from the post-anesthesia care unit.
Alternative Procedures
You may choose not to take part in this research study.
Conﬁdentiality
Any information collected during this study that can identify you by name will be kept conﬁdential. 
We will do everything we can to keep your data secure, however, complete conﬁdentiality cannot be 
promised. Despite all of our efforts, unanticipated problems, such as a stolen computer may occur, 
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although it is highly unlikely. The research ﬁle that links your name to the code number will be kept 
in a locked ﬁle cabinet and only the investigator and study staff will have access to the ﬁle. The 
following individuals and/or agencies will be able to look at and copy your research records: - The 
investigator, study staff and other medical professionals who may be evaluating the study - 
Authorities from Columbia University and New York Presbyterian Hospital, including the 
Institutional Review Board ('IRB') - The United States Food and Drug Administration ('FDA') and/or 
the Ofﬁce of Human Research Protections ('OHRP') and external, exclusive contractors who may be 
reviewing compliance with research policies. 
Research Related Injuries
Taking part in this research study may result in injury or harm to you. In the event of an injury 
resulting from your participation in this study, you should seek appropriate medical care and inform 
the study doctor. In the event of an emergency you should go to an emergency room. If you are 
injured or harmed as a result of participating in the study and receive medical care through the 
NewYork-Presbyterian Hospital (NYPH), a Columbia doctor, or any other health provider, you will 
be sent a bill for whatever medical care you receive. All or part of your bill may be paid by your 
health insurance. Columbia University and NewYork-Presbyterian Hospital (NYPH) are not offering 
to provide you the drug/device after the termination of the study or to pay you for pain, worry, lost 
income, the cost of your medical care or non-medical care costs that might occur as a result of your 
taking part in this study. However, you do not waive any of your legal rights in signing this form.
Compensation
You will not receive any payment or other compensation for taking part in this study.
Additional Costs
Taking part in this study will not involve additional costs to you. You and/or your insurance company 
will have to pay for any costs that are part of your regular medical care.
Voluntary Participation
Taking part in this study is your choice. You can decide not to take part in or stop being in the study at 
any time. Your choice will not affect the treatment you receive from doctors and staff at Columbia 
University Medical Center and New York Presbyterian Hospital.
Additional Information
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.
S. Law. This Web site will not include information that can identify you. At most, the Web site will 
include a summary of the results. You can search this Web site at any time
Signature
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Study Subject
Print Name____________________Signature____________________Date__________
Person Obtaining Consent
Print Name____________________Signature____________________Date__________
Subject Name
Print Name____________________
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IRB Approval Date: 11/13/2019
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