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{{Short description|Chemical compound}}
{{Drugbox
{{Drugbox
| Verifiedfields = changed
| Verifiedfields = changed
| verifiedrevid = 447573765
| verifiedrevid = 458285562
<!-- Clinical data -->
| IUPAC_name = Ancrod, Ophidian l-amino-acid oxidase (l-amino-acid oxygen:oxidoreductase, deaminating)
| tradename =

<!--Clinical data-->
<!-- Identifiers -->
| CAS_number_Ref = {{cascite|changed|??}}
| tradename =
| CAS_number = 9046-56-4

<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = <!-- blanked - oldvalue: 9046-56-4 -->
| ATC_prefix = B01
| ATC_prefix = B01
| ATC_suffix = AD09
| ATC_suffix = AD09
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| KEGG = D02938
| KEGG = D02938
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = NA
| ChemSpiderID = none
| PubChem=347909946

<!--Chemical data-->
<!-- Chemical data -->
}}
}}
{{Infobox nonhuman protein
'''Ancrod''' (current brand name: '''Viprinex''') is a [[defibrinogenating]] agent derived from the [[venom]] of the [[Malayan pit viper]]. Defibrinogenating blood produces an [[anticoagulant]] effect. Ancrod is not approved or marketed in any country, but is being investigated as a stroke treatment in worldwide [[clinical trial]]s. In January 2005, the [[Food and Drug Administration (United States)|U.S. Food and Drug Administration]] (FDA) granted '[[FDA Fast Track Development Program|fast-track status]]' for investigating ancrod use in patients suffering from acute [[ischemic stroke]], a life threatening condition caused by the blockage of blood vessels supplying blood and oxygen to portions of the brain, for which phase III trials are being conducted.
|Name=Thrombin-like enzyme ancrod
|Organism=Calloselasma rhodostoma
|UniProt=P26324
}}
{{Infobox nonhuman protein
|Name=Thrombin-like enzyme ancrod-2
|Organism=Calloselasma rhodostoma
|UniProt=P47797
}}
'''Ancrod''' (current brand name: '''Viprinex''') is a [[defibrinogenating agent]] derived from the [[venom]] of the [[Malayan pit viper]]. Defibrinogenating blood produces an [[anticoagulant]] effect. Ancrod is not approved or marketed in any country. It is a [[thrombin]]-like [[serine protease]].<ref>{{cite journal | vauthors = Macheroux P, Seth O, Bollschweiler C, Schwarz M, Kurfürst M, Au LC, Ghisla S | title = L-amino-acid oxidase from the Malayan pit viper Calloselasma rhodostoma. Comparative sequence analysis and characterization of active and inactive forms of the enzyme | journal = European Journal of Biochemistry | volume = 268 | issue = 6 | pages = 1679–86 | date = March 2001 | pmid = 11248687 | doi = 10.1046/j.1432-1327.2001.02042.x | url = http://nbn-resolving.de/urn:nbn:de:bsz:352-opus-51540 | doi-access = free }}</ref>


==Medical use==
== Marketing history ==
As of 2017 ancrod was not marketed for any medical use.<ref>{{cite web|title=Ancrod|url=http://adisinsight.springer.com/drugs/800004881|publisher=AdisInsight|access-date=5 February 2017|language=en}}</ref>


===Pregnancy===
Under the brand name Arwin, ancrod was marketed for several decades in [[Germany]] and [[Austria]], until it was withdrawn in the 1980s. Arwin was a brand name of Knoll Pharma. Neurobiological Technologies, Inc., currently holds the worldwide rights to ancrod under the brand name Viprinex. Previously, the rights to Viprinex were held by Empire Pharmaceuticals, Inc., [[Abbott Laboratories]], and Knoll AG, developers of this investigational drug.
Category X : Ancrod was not found to be [[teratogenic]] in animal studies, but some [[fetal]] deaths occurred as a result of [[placental hemorrhages]] in animals given high doses; therefore, it should not be used during pregnancy as the defibrinogenation mechanism of ancrod might be expected to interfere with the normal implantation of the fertilized egg.

On 1 August 2005, Neurobiological Technologies, Inc. (NTI) agreed with Nordmark Arzneimittel GmbH & Co KG (Nordmark) and Baxter Pharmaceutical Solutions, LLC (Baxter) to manufacture, fill and package Viprinex for NTI's Phase III clinical trials in acute ischemic stroke. Nordmark will manufacture the biological [[active ingredient]], ancrod.

==Chemistry and pharmacology==

Ancrod has a triple mode of action. The exact structure and chemical data such as molecular weight are unknown, but it has been elaborated that the [[glycosylation]] of the [[molecule]] is an important factor. Glycosylation is remarkably homogenous with the major [[oligosaccharide]] accounting for approximately 90% of the total sugar content. Some [[in vitro]] reactions have been explored in detail (see ref. #2, www.blckwell-synergy). It was found that ancrod's actions are [[FAD]] dependent and that the substance has interesting [[apoptotic]] properties (causing programmed cell death), which remain to be explored.
Ancrod is prepared from the crude [[venom]] of the Malayan pit [[Viperidae|viper]] (Agkistrodon rhodostoma, also termed Calloselasma rhodostoma) and belongs to the group of [[proteolytic]] [[enzyme]]s. Ancrod may also be found in the venom of many venomous snakes (crotalids, elapids and viperids) in general, but the Malayan pit viper is most suitable due to a high concentration of ancrod in its venom. For its preparation a snake farm, very skilled and well trained staff (for milking the highly venomous snakes), and special production facilities are required to purify the enzyme.

The [[Biological_half-life|half-life]] of ancrod is 3 to 5 hours and the drug is cleared from [[blood plasma]], mainly [[renally]].

Due to its special mode of action (see below) and its price, Arwin was never been used as 'normal' anticoagulant such as [[heparin]], but only for the symptomatic treatment of moderate to severe forms of peripheral arterial [[circulatory disorders]] such as those resulting from years of heavy smoking and/or [[arteriosclerosis]].

The substance is intended for [[parenteral]], namely [[subcutaneous]] (s.c.) injection and [[intravenous]] (i.v.) infusion, and indirectly inhibits [[wikt:aggregation|aggregation]], [[adhesion]], and release of [[thrombocytes]] mediated through the action of a fibrinogen degradation product (FDP). It also cleaves and therefore inactivates a significant part of circulating plasma [[fibrinogen]]. Fibrinogen is often found in increased concentrations in arteriae with impaired circulation. This leads to a pathologically increased blood [[viscosity]] and thereby to a worsening of symptoms of the circulation disorder (more intense pain, decreased mobility of the limb and decreased temperature, need for partial or even total limb [[amputation]]). The blood viscosity in patients receiving ancrod is progressively reduced by 30 to 40% of the pretreatment levels. The decreased viscosity is directly attributable to lowered fibrinogen levels and leads to important improvements in blood flow and [[perfusion]] of the [[microcirculation]]. [[Erythrocyte]] flexibility is not affected by normal doses of ancrod. The [[rheological]] changes are readily maintained and the viscosity approaches pretreatment values very slowly (within about 10 days) after stopping ancrod. One of the cleavage fibrinogen products, termed 'desAA-Fibrin', acts as [[Cofactor (biochemistry)|cofactor]] for the [[Tissue plasminogen activator|tPA]]-induced [[plasminogen]] activation and an increased [[fibrinolysis]] results in return (profibrinolytic activity of ancrod).

Ancrod decreases the blood viscosity in affected arteries, leads to less intense pain, improves physical limb mobility, and facilitates physical and [[ergo therapy]]. Finally, ancrod decreases the likelihood of local thrombotic events.

These mechanisms also account for ancrod's activity in other diseases.

Effects on other [[clotting factors]]: Unlike [[thrombin]], ancrod does not directly activate [[Factor XIII]], nor does it produce [[platelet aggregation]] nor cause the release of [[adenosine diphosphate|ADP]], [[adenosine triphosphate|ATP]], [[potassium]], or [[serotonin]] from platelets. Platelet counts and survival time remain normal during ancord therapy.

==Indications==
===Historical===
For the treatment of established [[deep vein thrombosis]]; central retinal and branch vein thrombosis; [[priapism]]; [[pulmonary hypertension]] of embolic origin; [[embolism]] after insertion of prosthetic [[cardiac valves]]; rethrombosis after thrombolytic therapy and rethrombosis after vascular surgery. It is also indicated for the prevention of deep venous thrombosis after repair of the fractured neck of a femur.

For the treatment of moderate and severe chronic circulatory disorders of peripheral arteries (e.g., [[arteriosclerosis]] obliterans, [[thromboangiitis obliterans]], [[diabetic microangiopathy]] and [[Raynaud's phenomenon]]).

Ancrod has been shown to be useful for maintaining anticoagulation in the presence of [[Heparin-induced thrombocytopenia]] (HIT) and thrombosis.

Currently, this drug is not approved nor available. It is being investigated in clinical trials for stroke.

===Studies in early ischemic stroke===

In a multicenter, parallel, group sequential, randomized, [[double-blind]], [[placebo-controlled]] German study of efficacy and safety of i.v. ancrod given within 6 hours after the onset of acute, ischemic stroke and continued for 5 days (called ESTAT study), the early findings for 800 patients were positive, but as the study was expanded to 1,600 patients, placebo was found to be more effective than ancrod and the study was abruptly terminated, mainly because the [[mortality rate]] in the ancrod group was higher. The smaller American study 'Stroke Treatment with Ancrod Trial (STAT)' confirmed the negative outcome for ischemic stroke. In these studies, patients received a multi-day infusion of Viprinex designed to maintain patients’ fibrinogen level within a targeted range. Currently, a new dosing strategy is being investigated in two international phase III trials as part of the 'Ancrod Stroke Program (ASP).' Each of these studies will enroll 650 patients and assess whether a brief, relatively rapid ancrod infusion with no maintenance dosing will be effective and safe.The ANCROD STROKE PROGRAM, was terminated in Jan 2009 for futility and NTI has terminated further development of the agent


==Contraindications and precautions==
==Contraindications and precautions==
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* [[Renal stones]] (increased likelihood of significant urological bleeding).
* [[Renal stones]] (increased likelihood of significant urological bleeding).
* Severe and uncontrolled [[arterial hypertension]].
* Severe and uncontrolled [[arterial hypertension]].
* Active [[pulmonary tuberculosis]].
* Active [[pulmonary tuberculosis]].
* Impaired [[fibrinolysis]].
* Impaired [[fibrinolysis]].
* Severe [[liver disease]].
* Severe [[liver disease]].
* Manifest or impending [[Shock (medical)|shock]].
* Manifest or impending [[Shock (circulatory)|shock]].
* I.M.-Injection : Ancrod should not be injected i.m., because of rapid induction of neutralizing [[antibodies]] and therefore [[drug resistance]].
* I.M.-Injection : Ancrod should not be injected i.m., because of rapid induction of neutralizing [[antibodies]] and thus [[drug resistance]].


===Pregnancy===
==Side effects==
In clinical trials for [[ischemic stroke]], ancrod increased the risk of [[intracerebral hemorrhage]].<ref name=Cochrane2012/>
Category X : Ancrod was not found to be [[teratogenic]] in animal studies, but some [[fetal]] deaths occurred as a result of [[placental hemorrhages]] in animals given high doses; therefore, it should not be used during pregnancy as the defibrinogenation mechanism of ancrod might be expected to interfere with the normal implantation of the fertilized egg.


==Side effects==
* Hypersensitivity reactions : Local or generalized [[skin reactions]] ([[rash]] and [[urticaria]]); appearance of neutralizing [[antibodies]] to ancrod with partial or total loss of ancrod activity (drug resistance).
* Hypersensitivity reactions : Local or generalized [[skin reactions]] ([[rash]] and [[urticaria]]); appearance of neutralizing [[antibodies]] to ancrod with partial or total loss of ancrod activity (drug resistance).
* Sometimes pain at injection site (normally mild). This side effect may be, if necessary, treated with local or oral [[antihistaminic]] drugs (e.g., [[clemastine]], or [[diphenhydramine]]). Bleeding at injection site, [[thrombophlebitis]] at local veins, and (paradoxical) arterial thrombotic events.
* Sometimes pain at injection site (normally mild). This side effect may be, if necessary, treated with local or oral [[antihistaminic]] drugs (e.g., [[clemastine]], or [[diphenhydramine]]). Bleeding at injection site, [[thrombophlebitis]] at local veins, and (paradoxical) arterial thrombotic events.
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[[Thrombocytopenia]] as side effect has never been noticed with ancrod in contrast to heparin.
[[Thrombocytopenia]] as side effect has never been noticed with ancrod in contrast to heparin.


It was not found to be of much use in the clinical trials. ''In vitro'' experiments show that it may actually clot blood.<ref>{{cite journal | vauthors = Nielsen VG | title = Ancrod revisited: viscoelastic analyses of the effects of Calloselasma rhodostoma venom on plasma coagulation and fibrinolysis | journal = Journal of Thrombosis and Thrombolysis | volume = 42 | issue = 2 | pages = 288–93 | date = August 2016 | pmid = 26905070 | doi = 10.1007/s11239-016-1343-6 | s2cid = 23087988 }}</ref>
==Availablility==

==Pharmacology==
{{Unreferenced section|date=October 2022}}

Ancrod has a triple mode of action. It was found that ancrod's actions are [[flavin adenine dinucleotide|FAD]] dependent and that the substance has interesting [[apoptotic]] properties (causing programmed cell death), which remain to be explored.

The [[Biological half-life|half-life]] of ancrod is 3 to 5 hours and the drug is cleared from [[blood plasma]], mainly [[renally]].

Due to its special mode of action (see below) and its price, Arwin has never been used as 'normal' anticoagulant such as [[heparin]], but only for the symptomatic treatment of moderate to severe forms of peripheral arterial [[circulatory disorders]] such as those resulting from years of heavy smoking and/or [[arteriosclerosis]].

The substance is intended for [[Subcutaneous injection|subcutaneous]] injection and [[intravenous]] infusion, and indirectly inhibits [[wikt:aggregation|aggregation]], [[adhesion]], and release of [[thrombocytes]] mediated through the action of a fibrinogen degradation product (FDP). It also cleaves and therefore inactivates a significant part of circulating plasma [[fibrinogen]]. Fibrinogen is often found in increased concentrations in arteriae with impaired circulation. This leads to a pathologically increased blood [[viscosity]] and thereby to a worsening of symptoms of the circulation disorder (more intense pain, decreased mobility of the limb and decreased temperature, need for partial or even total limb amputation). The blood viscosity in patients receiving ancrod is progressively reduced by 30 to 40% of the pretreatment levels. The decreased viscosity is directly attributable to lowered fibrinogen levels and leads to important improvements in blood flow and [[perfusion]] of the [[microcirculation]]. [[Erythrocyte]] flexibility is not affected by normal doses of ancrod. The [[rheological]] changes are readily maintained and the viscosity approaches pretreatment values very slowly (within about 10 days) after stopping ancrod. One of the cleavage fibrinogen products, termed 'desAA-Fibrin', acts as [[Cofactor (biochemistry)|cofactor]] for the [[Tissue plasminogen activator|tPA]]-induced [[plasminogen]] activation and an increased [[fibrinolysis]] results in return (profibrinolytic activity of ancrod).

Ancrod decreases the blood viscosity in affected arteries, leads to less intense pain, improves physical limb mobility, and facilitates physical and [[ergo therapy]]. Finally, ancrod decreases the likelihood of local thrombotic events. These mechanisms also account for ancrod's activity in other diseases.

Effects on other [[clotting factors]]: Unlike [[thrombin]], ancrod does not directly activate [[Factor XIII]], nor does it produce [[platelet aggregation]] nor cause the release of [[adenosine diphosphate|ADP]], [[adenosine triphosphate|ATP]], [[potassium]], or [[serotonin]] from platelets. Platelet counts and survival time remain normal during ancrod therapy.

==Chemistry==
Ancrod was originally isolated from the [[venom]] of the Malayan pit [[Viperidae|viper]] (''Calloselasma rhodostoma'', formerly ''Agkistrodon rhodostoma'') and is a [[serine protease]].<ref name=Asadi2014rev>{{cite journal | vauthors = Asadi H, Yan B, Dowling R, Wong S, Mitchell P | title = Advances in medical revascularisation treatments in acute ischemic stroke | journal = Thrombosis | volume = 2014 | pages = 714218 | date = 2014 | pmid = 25610642 | pmc = 4293866 | doi = 10.1155/2014/714218 | doi-access = free }}</ref> It is one of the [[Venombin A]] enzymes. Two genes encoding for such enzymes have been found in the viper genome.<ref name=pmid1544412>{{cite journal | vauthors = Burkhart W, Smith GF, Su JL, Parikh I, LeVine H | title = Amino acid sequence determination of ancrod, the thrombin-like alpha-fibrinogenase from the venom of Akistrodon rhodostoma | journal = FEBS Letters | volume = 297 | issue = 3 | pages = 297–301 | date = February 1992 | pmid = 1544412 | doi = 10.1016/0014-5793(92)80559-Y | s2cid = 27571744 | doi-access = free }}</ref><ref name=pmid8373353>{{cite journal | vauthors = Au LC, Lin SB, Chou JS, Teh GW, Chang KJ, Shih CM | title = Molecular cloning and sequence analysis of the cDNA for ancrod, a thrombin-like enzyme from the venom of Calloselasma rhodostoma | journal = The Biochemical Journal | volume = 294 | issue = 2 | pages = 387–90 | date = September 1993 | pmid = 8373353 | pmc = 1134466 | doi = 10.1042/bj2940387 }}</ref>

The form used in clinical trials was not made recombinantly, but was purified from harvested venom.<ref name=CNNmoney2006>{{cite news| vauthors = Smith A |title=California biotech looking in snakes' mouths for stroke drug - Feb. 24, 2006|url=https://money.cnn.com/2006/02/24/news/companies/snake/|work=CNN Money|date=February 24, 2006}}</ref><ref name=Supply>{{cite web|title=Exhibit 10.1: Cooperation and Supply Agreement|url=https://www.sec.gov/Archives/edgar/data/918112/000119312505102720/dex101.htm|publisher=NTI via SEC Edgar|access-date=5 February 2017}}</ref>

== History ==
Under the brand name Arwin, ancrod was marketed for several decades in [[Germany]] and [[Austria]], until it was withdrawn in the 1980s. Arwin was a brand name of [[Knoll Pharma]].

In 2001 Knoll was acquired by [[Abbott Laboratories]], and in 2002 Abbott licensed the rights to ancrod to Empire Pharmaceuticals, a startup that included a Knoll employee who had worked on ancrod.<ref>{{cite web|title=Form 10-K For the fiscal year ended June 30, 2007|url=https://www.sec.gov/Archives/edgar/data/918112/000119312507200761/d10k.htm|publisher=NTI via SEC Edgar|date=September 13, 2007}}</ref><ref>{{cite web|title=Exhibit 10.18 License Agreement between Empire and Abbott, March 29, 2002|url=https://www.lawinsider.com/contracts/3ujCdKUUEBx9HEBd6Dkba7/neurobiological-technologies-inc/918112/2005-09-28|publisher=Law Insider}}</ref> {{rp|5}} In 2004 Empire was acquired by [[Neurobiological Technologies]].<ref name=PharmaLetter2004>{{cite news|title=Neurobiological Tech buys Empire Pharma|url=http://www.thepharmaletter.com/article/neurobiological-tech-buys-empire-pharma|work=The Pharma Letter|date=July 26, 2004|language=en}}</ref> NTI also acquired a lot of unpurified venom in the acquisition, and had that purified for use in its clinical trials.<ref name=CNNmoney2006/><ref name=Supply/>

The failure of ancrod in the 6-hour window for ischemic stroke trial in 2008 led to cuts in staff, an effort to sell off the company's assets, and finally to the dissolution of NTI in August 2009.<ref name=Fierce2008/><ref>{{cite news| vauthors = Brown SE, Leuty R |title=Neurobiological Technologies to dissolve |url= http://www.bizjournals.com/sanfrancisco/stories/2009/08/31/daily9.html |work=San Francisco Business Times |date=August 31, 2009 }}</ref>

==Society and culture==
Viprinex is not currently approved or available.
Viprinex is not currently approved or available.


==References==
==Research==
For the treatment of established [[deep vein thrombosis]]; central retinal and branch vein thrombosis; [[priapism]]; [[pulmonary hypertension]] of embolic origin; [[embolism]] after insertion of prosthetic [[cardiac valves]]; rethrombosis after thrombolytic therapy and rethrombosis after vascular surgery. It is also indicated for the prevention of deep venous thrombosis after repair of the fractured neck of a femur.
{{No footnotes|date=May 2009}}
* H. P. T. Ammon (Editor) : Arzneimittelneben- und -wechselwirkungen, Wissenschaftliche Verlagsgesellschaft mbH, Stuttgart (4th. ed.), 2001, ISBN 3-8047-1717-9, in German


For the treatment of moderate and severe chronic circulatory disorders of peripheral arteries (e.g., [[arteriosclerosis]] obliterans, [[thromboangiitis obliterans]], [[diabetic microangiopathy]] and [[Raynaud's phenomenon]]).
* {{cite journal |author=Geyer A, Fitzpatrick TB, Pawelek PD, ''et al.'' |title=Structure and characterization of the glycan moiety of L-amino-acid oxidase from the Malayan pit viper Calloselasma rhodostoma |journal=Eur. J. Biochem. |volume=268 |issue=14 |pages=4044&ndash;53 |year=2001 |pmid=11453999 |doi= 10.1046/j.1432-1327.2001.02321.x|url=http://www.blackwell-synergy.com/servlet/useragent?func=synergy&synergyAction=showAbstract&doi=10.1046/j.1432-1327.2001.02321.x}}
* http://archiv.ub.uni-heidelberg.de/volltextserver/volltexte/2003/3368/pdf/diss03-20.pdf (Some results of clinical research) - in German
* http://www.uni-leipzig.de/forsch00/49000/49219.htm (negative study results in ischemic strike), in German
* http://www.ntii.com/products/viprinex.shtml (phase III studies in the USA regarding ischemic stroke)
* http://www.prohostonline.com/ImpactingNews/IN%201%2028%2005.pdf (FDA grants fast-track status for indication ischemic stroke)
* http://www.rxmed.com/b.main/b2.pharmaceutical/b2.1.monographs/CPS-%20Monographs/CPS-%20(General%20Monographs-%20V)/VIPRINEX.html (scientific information on Viprinex)
* http://www.findarticles.com/p/articles/mi_m0DHC/is_8_17/ai_n14792504 (marketing agreement Neurobiological - Nordmark - Baxter)


Ancrod has been shown to be useful for maintaining anticoagulation in the presence of [[Heparin-induced thrombocytopenia]] (HIT) and thrombosis.
* {{cite journal |author=Sherman DG, Atkinson RP, Chippendale T, ''et al.'' |title=Intravenous ancrod for treatment of acute ischemic stroke: the STAT study: a randomized controlled trial. Stroke Treatment with Ancrod Trial |journal=JAMA |volume=283 |issue=18 |pages=2395&ndash;403 |year=2000 |pmid=10815082 |doi=10.1001/jama.283.18.2395}}


A small study compared to ancrod to [[heparin]] in preventing [[thrombosis]] when given to people undergoing arterial graft surgery to treat [[peripheral arterial disease]] and found little difference between the two agents.<ref>{{cite journal | vauthors = Geraghty AJ, Welch K | title = Antithrombotic agents for preventing thrombosis after infrainguinal arterial bypass surgery | journal = The Cochrane Database of Systematic Reviews | issue = 6 | pages = CD000536 | date = June 2011 | volume = 2011 | pmid = 21678330 | doi = 10.1002/14651858.CD000536.pub2 | pmc = 7047373 }}</ref>
* {{cite journal |author= |title=Ancrod for the treatment of acute ischemic brain infarction. The Ancrod Stroke Study Investigators |journal=Stroke |volume=25 |issue=9 |pages=1755&ndash;9 |year=1994 |pmid=8073455 |doi=10.1161/01.STR.25.9.1755}}


Ancrod was intensively studied in [[ischemic stroke]], starting at least by the early 1990s.<ref>{{cite journal | title = Ancrod for the treatment of acute ischemic brain infarction. The Ancrod Stroke Study Investigators | journal = Stroke | volume = 25 | issue = 9 | pages = 1755–9 | date = September 1994 | pmid = 8073455 | doi = 10.1161/01.STR.25.9.1755 | doi-access = free }}</ref> An RCT called "STAT" was published in 2000; it included 500 subjects and ancrod or placebo was administered within three hours of the stroke. Ancrod showed modest benefits but a trend toward increased [[intracranial haemorrhage]].<ref name=Asadi2014rev/><ref>{{cite journal | vauthors = Sherman DG, Atkinson RP, Chippendale T, Levin KA, Ng K, Futrell N, Hsu CY, Levy DE | title = Intravenous ancrod for treatment of acute ischemic stroke: the STAT study: a randomized controlled trial. Stroke Treatment with Ancrod Trial | journal = JAMA | volume = 283 | issue = 18 | pages = 2395–403 | date = May 2000 | pmid = 10815082 | doi = 10.1001/jama.283.18.2395 | doi-access = }}</ref> A clinical trial published in 2006 found no benefit if ancrod was given within a wider 6 hour treatment window.<ref>{{cite journal | vauthors = Hennerici MG, Kay R, Bogousslavsky J, Lenzi GL, Verstraete M, Orgogozo JM | title = Intravenous ancrod for acute ischaemic stroke in the European Stroke Treatment with Ancrod Trial: a randomised controlled trial | journal = Lancet | volume = 368 | issue = 9550 | pages = 1871–8 | date = November 2006 | pmid = 17126719 | doi = 10.1016/S0140-6736(06)69776-6 | s2cid = 1483950 }}</ref> Another trial was launched to explore the 6 hour window, but it was halted early in 2008 when an independent review committee looked at the interim data and found no signal of benefit.<ref name=Asadi2014rev/><ref name=Cochrane2012>{{cite journal | vauthors = Hao Z, Liu M, Counsell C, Wardlaw JM, Lin S, Zhao X | title = Fibrinogen depleting agents for acute ischaemic stroke | journal = The Cochrane Database of Systematic Reviews | issue = 3 | pages = CD000091 | date = March 2012 | pmid = 22419274 | doi = 10.1002/14651858.CD000091.pub2 }}</ref><ref name=Fierce2008>{{cite news| vauthors = Carroll J |title=Neurobiological Tech halts enrollment, prepares cuts|url=http://www.fiercebiotech.com/biotech/neurobiological-tech-halts-enrollment-prepares-cuts|work=FierceBiotech|date=December 17, 2008|language=en}}</ref>
* {{cite journal |author=Hennerici MG, Kay R, Bogousslavsky J, Lenzi GL, Verstraete M, Orgogozo JM |title=Intravenous ancrod for acute ischaemic stroke in the European Stroke Treatment with Ancrod Trial: a randomised controlled trial |journal=Lancet |volume=368 |issue=9550 |pages=1871&ndash;8 |year=2006 |pmid=17126719 |doi=10.1016/S0140-6736(06)69776-6}}


==External links==
== References ==
{{More footnotes|date=May 2009}}
* {{MeshName|Ancrod}}
{{reflist}}

== See also ==
* [[Batroxobin]], another medical snake venom serine protease

== External links ==
* {{cite web|title="Eye On" report: Neurobiological Technologies, Inc.|url=http://www.prohostonline.com/ImpactingNews/IN%201%2028%2005.pdf|publisher=Prohost Research|date=January 28, 2005}}


{{Serine endopeptidases}}
{{Serine endopeptidases}}
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[[Category:Antithrombotic enzymes]]
[[Category:Antithrombotic enzymes]]
[[Category:Abandoned drugs]]

[[fr:Ancrod]]
[[pt:Ancrodo]]
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