Perioperative pharmacokinetic-guided factor VIII concentrate dosing in haemophilia (OPTI-CLOT trial): an open-label, multicentre, randomised, controlled trial

OPTI-CLOT study group

doi:10.1016/S2352-3026(21)00135-6

Perioperative pharmacokinetic-guided factor VIII concentrate dosing in haemophilia (OPTI-CLOT trial): an open-label, multicentre, randomised, controlled trial

OPTI-CLOT study group

Research output: Contribution to journal › Article › Academic › peer-review

11 Citations (Scopus)

Abstract

Background: Dosing of replacement therapy with factor VIII concentrate in patients with haemophilia A in the perioperative setting is challenging. Underdosing and overdosing of factor VIII concentrate should be avoided to minimise risk of perioperative bleeding and treatment costs. We hypothesised that dosing of factor VIII concentrate on the basis of a patient's pharmacokinetic profile instead of bodyweight, which is standard treatment, would reduce factor VIII consumption and improve the accuracy of attained factor VIII levels. Methods: In this open-label, multicentre, randomised, controlled trial (OPTI-CLOT), patients were recruited from nine centres in Rotterdam, Groningen, Utrecht, Nijmegen, The Hague, Leiden, Amsterdam, Eindhoven, and Maastricht in The Netherlands. Eligible patients were aged 12 years or older with severe or moderate haemophilia A (severe haemophilia was defined as factor VIII concentrations of <0·01 IU/mL, and moderate haemophilia as 0·01–0·05 IU/mL), without factor VIII inhibitors, and planned for elective low or medium risk surgery as defined by surgical risk score. Patients were randomly assigned (1:1) using a web-based randomisation system and treatment minimisation, stratified by method of administration of factor VIII concentrate (continuous infusion vs bolus administration) and risk level of surgery (low and medium risk surgery), to the pharmacokinetic-guided or standard treatment group. The primary endpoint was total amount of infused factor VIII concentrate (IU per kg bodyweight) during perioperative period (from day of surgery up to 14 days after surgery). Analysis was by intention to treat and the safety analysis population comprised all participants who underwent surgery with factor VIII concentrate. This study is registered with the Netherlands Trial Registry, NL3955, and is now closed to accrual. Findings: Between May 1, 2014, and March 1, 2020, 98 patients were assessed for eligibility and 66 were enrolled in the trial and randomly assigned to the pharmacokinetic-guided treatment group (34 [52%]) or the standard treatment group (32 [48%]). Median age was 49·1 years (IQR 35·0 to 62·1) and all participants were male. No difference was seen in consumption of factor VIII concentrate during the perioperative period between groups (mean consumption of 365 IU/kg [SD 202] in pharmacokinetic-guided treatment group vs 379 IU/kg [202] in standard treatment group; adjusted difference −6 IU/kg [95% CI −88 to 100]). Postoperative bleeding occurred in six (18%) of 34 patients in the pharmacokinetic-guided treatment group and three (9%) of 32 in the standard treatment group. One grade 4 postoperative bleeding event occurred, which was in one (3%) patient in the standard treatment group. No treatment-related deaths occurred. Interpretation: Although perioperative pharmacokinetic-guided dosing is safe, it leads to similar perioperative factor VIII consumption when compared with standard treatment. However, pharmacokinetic-guided dosing showed an improvement in obtaining factor VIII concentrations within the desired perioperative factor VIII range. These findings provide support to further investigation of pharmacokinetic-guided dosing in perioperative haemophilia care. Funding: Dutch Research Council (NWO)-ZonMw and Takeda.

Original language	English
Pages (from-to)	e492-e502
Journal	The Lancet Haematology
Volume	8
Issue number	7
DOIs	https://doi.org/10.1016/S2352-3026(21)00135-6
Publication status	Published - Jul 2021

Bibliographical note

Funding Information:
This study is part of the OPTI-CLOT trial, which was funded by a governmental grant from NWO-ZonMw (project number 836011011) and co-financed by an unrestricted investigator-initiated research grant from Baxter/Shire/Baxalta/Takeda (grant number GHOL 6238). This Article is written on behalf of the international multicentre OPTI-CLOT and To WiN studies that aim to implement a pharmacokinetic-guided approach for the treatment of bleeding disorders using population pharmacokinetic models for desmopressin, factor concentrates, and other alternative drugs. A complete list of the members of the OPTI-CLOT research programme is in the appendix (p 3) . We thank all patients and family members who participated in this trial. We also thank all haemophilia teams, nurses, and research coordinators for their indispensable assistance. Furthermore, we thank D Nieboer for his statistical advice, I van Vliet for trial support, and J M Heijdra and L M Schütte for their help and assistance during the trial period.

Funding Information:
REGS has received research support from Bayer, Baxalta, CSL Behring, Novo Nordisk, Pfizer, Sobi, and Sanquin. FJMvdM has received grants from Bayer, CSL Behring, Novo Nordisk, Octapharma, Pfizer, Roche, Takeda, and Sobi for the development of a registry of Hemophilia patients in the Netherlands (HemoNED). KF has received unrestricted research grants from CSL Behring, Sobi, and Novo Nordisk, and her institution has received consultancy fees from Grifols, Takeda, Novo Nordisk, and Roche. MC has received research grants from Bayer, CSL Behring, Roche, UniQure, and Novo Nordisk. FWGL has received unrestricted research grants from CSL Behring, Shire/Takeda, Sobi, and UniQure; is a consultant for UniQure, Novo Nordisk, Biomarin and Shire, from which the fees go to their institution; has received travel support from Sobi; and is a member of the data safety and monitoring board for a study sponsored by Roche. KM has received research support from Bayer and Alexion and consulting fees from UniQure, from which all fees go to their institution. RAAM has served as an advisor for Bayer, CSL Behring, Merck Sharp & Dohme, Shire, and Zeria, with all honoraria and fees paid to their department at their institution), and has received unrestricted research grants from Bayer, CSL Behring, and Shire. MHC has received grants from the governmental research institutes Dutch Research Institute (NWO), ZonMW, Innovation fund, NWO-NWA; unrestricted investigator-initiated research grants and educational and travel funding from Pfizer, Baxter/Baxalta/Shire, Bayer Schering Pharma, CSL Behring, Sobi Biogen, Novo Nordisk, Novartis, and Nordic Pharma; and has served as a member on steering boards of Roche, Novartis, and Bayer, with all grants, awards, and fees received going to their institution. JGvdB has received funding for educational activities from Bayer and Novo Nordisk. IvM has received research grants from Sobi and CSL Behring. All other authors declare no competing interests.

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© 2021 Elsevier Ltd

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EMC MM-02-54-03

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10.1016/S2352-3026(21)00135-6

https://research.rug.nl/en/publications/perioperative-pharmacokinetic-guided-factor-viii-concentrate-dosi

Cite this

@article{a130e17240894bbe91008e28dbcde12c,

title = "Perioperative pharmacokinetic-guided factor VIII concentrate dosing in haemophilia (OPTI-CLOT trial): an open-label, multicentre, randomised, controlled trial",

abstract = "Background: Dosing of replacement therapy with factor VIII concentrate in patients with haemophilia A in the perioperative setting is challenging. Underdosing and overdosing of factor VIII concentrate should be avoided to minimise risk of perioperative bleeding and treatment costs. We hypothesised that dosing of factor VIII concentrate on the basis of a patient's pharmacokinetic profile instead of bodyweight, which is standard treatment, would reduce factor VIII consumption and improve the accuracy of attained factor VIII levels. Methods: In this open-label, multicentre, randomised, controlled trial (OPTI-CLOT), patients were recruited from nine centres in Rotterdam, Groningen, Utrecht, Nijmegen, The Hague, Leiden, Amsterdam, Eindhoven, and Maastricht in The Netherlands. Eligible patients were aged 12 years or older with severe or moderate haemophilia A (severe haemophilia was defined as factor VIII concentrations of <0·01 IU/mL, and moderate haemophilia as 0·01–0·05 IU/mL), without factor VIII inhibitors, and planned for elective low or medium risk surgery as defined by surgical risk score. Patients were randomly assigned (1:1) using a web-based randomisation system and treatment minimisation, stratified by method of administration of factor VIII concentrate (continuous infusion vs bolus administration) and risk level of surgery (low and medium risk surgery), to the pharmacokinetic-guided or standard treatment group. The primary endpoint was total amount of infused factor VIII concentrate (IU per kg bodyweight) during perioperative period (from day of surgery up to 14 days after surgery). Analysis was by intention to treat and the safety analysis population comprised all participants who underwent surgery with factor VIII concentrate. This study is registered with the Netherlands Trial Registry, NL3955, and is now closed to accrual. Findings: Between May 1, 2014, and March 1, 2020, 98 patients were assessed for eligibility and 66 were enrolled in the trial and randomly assigned to the pharmacokinetic-guided treatment group (34 [52%]) or the standard treatment group (32 [48%]). Median age was 49·1 years (IQR 35·0 to 62·1) and all participants were male. No difference was seen in consumption of factor VIII concentrate during the perioperative period between groups (mean consumption of 365 IU/kg [SD 202] in pharmacokinetic-guided treatment group vs 379 IU/kg [202] in standard treatment group; adjusted difference −6 IU/kg [95% CI −88 to 100]). Postoperative bleeding occurred in six (18%) of 34 patients in the pharmacokinetic-guided treatment group and three (9%) of 32 in the standard treatment group. One grade 4 postoperative bleeding event occurred, which was in one (3%) patient in the standard treatment group. No treatment-related deaths occurred. Interpretation: Although perioperative pharmacokinetic-guided dosing is safe, it leads to similar perioperative factor VIII consumption when compared with standard treatment. However, pharmacokinetic-guided dosing showed an improvement in obtaining factor VIII concentrations within the desired perioperative factor VIII range. These findings provide support to further investigation of pharmacokinetic-guided dosing in perioperative haemophilia care. Funding: Dutch Research Council (NWO)-ZonMw and Takeda.",

author = "{van Moort}, Iris and Tim Preijers and {OPTI-CLOT study group} and Bukkems, {Laura H.} and Hazendonk, {Hendrika C.A.M.} and {van der Bom}, {Johanna G.} and {Laros-van Gorkom}, {Britta A.P.} and Beckers, {Erik A.M.} and Laurens Nieuwenhuizen and {van der Meer}, {Felix J.M.} and Paula Ypma and Michiel Coppens and Karin Fijnvandraat and Schutgens, {Roger E.G.} and Karina Meijer and Math{\^o}t, {Ron A.A.} and Cnossen, {Marjon H.} and Leebeek, {Frank W.G.} and Math{\^o}t, {Ron A.A.} and Kruip, {Marieke J.H.A.} and Suzanne Polinder and Janske Lock and Hazendonk, {Hendrika C.A.M.} and Heijdra, {Jessica M.} and Goedhart, {Marie C.H.J.} and {Al Arashi}, Wala and {De Jager}, {Nico C.B.} and Bukkems, {Laura H.} and Cloesmeijer, {Michael E.} and Alexander Janssen and Tamminga, {Rienk Y.J.} and Paul Brons and Schols, {Saskia E.M.} and Eikenboom, {Jeroen C.J.} and {Van der Meer}, {Felix J.M.} and Schutgens, {Roger E.G.} and Kathelijne Fischer and {Van Galen}, {Karin P.M.} and Beckers, {Erik E.A.M.} and Heubel-Moenen, {Floor C.J.I.} and Driessens, {Mari{\"e}tte H.E.} and {Van Vliet}, Ineke and Collins, {Peter W.} and Ri Liesner and Pratima Chowdary and Millar, {Carolyn M.} and Dan Hart and David Keeling",

note = "Funding Information: This study is part of the OPTI-CLOT trial, which was funded by a governmental grant from NWO-ZonMw (project number 836011011) and co-financed by an unrestricted investigator-initiated research grant from Baxter/Shire/Baxalta/Takeda (grant number GHOL 6238). This Article is written on behalf of the international multicentre OPTI-CLOT and To WiN studies that aim to implement a pharmacokinetic-guided approach for the treatment of bleeding disorders using population pharmacokinetic models for desmopressin, factor concentrates, and other alternative drugs. A complete list of the members of the OPTI-CLOT research programme is in the appendix (p 3) . We thank all patients and family members who participated in this trial. We also thank all haemophilia teams, nurses, and research coordinators for their indispensable assistance. Furthermore, we thank D Nieboer for his statistical advice, I van Vliet for trial support, and J M Heijdra and L M Sch{\"u}tte for their help and assistance during the trial period. Funding Information: REGS has received research support from Bayer, Baxalta, CSL Behring, Novo Nordisk, Pfizer, Sobi, and Sanquin. FJMvdM has received grants from Bayer, CSL Behring, Novo Nordisk, Octapharma, Pfizer, Roche, Takeda, and Sobi for the development of a registry of Hemophilia patients in the Netherlands (HemoNED). KF has received unrestricted research grants from CSL Behring, Sobi, and Novo Nordisk, and her institution has received consultancy fees from Grifols, Takeda, Novo Nordisk, and Roche. MC has received research grants from Bayer, CSL Behring, Roche, UniQure, and Novo Nordisk. FWGL has received unrestricted research grants from CSL Behring, Shire/Takeda, Sobi, and UniQure; is a consultant for UniQure, Novo Nordisk, Biomarin and Shire, from which the fees go to their institution; has received travel support from Sobi; and is a member of the data safety and monitoring board for a study sponsored by Roche. KM has received research support from Bayer and Alexion and consulting fees from UniQure, from which all fees go to their institution. RAAM has served as an advisor for Bayer, CSL Behring, Merck Sharp & Dohme, Shire, and Zeria, with all honoraria and fees paid to their department at their institution), and has received unrestricted research grants from Bayer, CSL Behring, and Shire. MHC has received grants from the governmental research institutes Dutch Research Institute (NWO), ZonMW, Innovation fund, NWO-NWA; unrestricted investigator-initiated research grants and educational and travel funding from Pfizer, Baxter/Baxalta/Shire, Bayer Schering Pharma, CSL Behring, Sobi Biogen, Novo Nordisk, Novartis, and Nordic Pharma; and has served as a member on steering boards of Roche, Novartis, and Bayer, with all grants, awards, and fees received going to their institution. JGvdB has received funding for educational activities from Bayer and Novo Nordisk. IvM has received research grants from Sobi and CSL Behring. All other authors declare no competing interests. Publisher Copyright: {\textcopyright} 2021 Elsevier Ltd",

year = "2021",

month = jul,

doi = "10.1016/S2352-3026(21)00135-6",

language = "English",

volume = "8",

pages = "e492--e502",

journal = "The Lancet Haematology",

issn = "2352-3026",

publisher = "Lancet Publishing Group",

number = "7",

}

TY - JOUR

T1 - Perioperative pharmacokinetic-guided factor VIII concentrate dosing in haemophilia (OPTI-CLOT trial)

T2 - an open-label, multicentre, randomised, controlled trial

AU - van Moort, Iris

AU - Preijers, Tim

AU - OPTI-CLOT study group

AU - Bukkems, Laura H.

AU - Hazendonk, Hendrika C.A.M.

AU - van der Bom, Johanna G.

AU - Laros-van Gorkom, Britta A.P.

AU - Beckers, Erik A.M.

AU - Nieuwenhuizen, Laurens

AU - van der Meer, Felix J.M.

AU - Ypma, Paula

AU - Coppens, Michiel

AU - Fijnvandraat, Karin

AU - Schutgens, Roger E.G.

AU - Meijer, Karina

AU - Mathôt, Ron A.A.

AU - Cnossen, Marjon H.

AU - Leebeek, Frank W.G.

AU - Mathôt, Ron A.A.

AU - Kruip, Marieke J.H.A.

AU - Polinder, Suzanne

AU - Lock, Janske

AU - Hazendonk, Hendrika C.A.M.

AU - Heijdra, Jessica M.

AU - Goedhart, Marie C.H.J.

AU - Al Arashi, Wala

AU - De Jager, Nico C.B.

AU - Bukkems, Laura H.

AU - Cloesmeijer, Michael E.

AU - Janssen, Alexander

AU - Tamminga, Rienk Y.J.

AU - Brons, Paul

AU - Schols, Saskia E.M.

AU - Eikenboom, Jeroen C.J.

AU - Van der Meer, Felix J.M.

AU - Schutgens, Roger E.G.

AU - Fischer, Kathelijne

AU - Van Galen, Karin P.M.

AU - Beckers, Erik E.A.M.

AU - Heubel-Moenen, Floor C.J.I.

AU - Driessens, Mariëtte H.E.

AU - Van Vliet, Ineke

AU - Collins, Peter W.

AU - Liesner, Ri

AU - Chowdary, Pratima

AU - Millar, Carolyn M.

AU - Hart, Dan

AU - Keeling, David

N1 - Funding Information: This study is part of the OPTI-CLOT trial, which was funded by a governmental grant from NWO-ZonMw (project number 836011011) and co-financed by an unrestricted investigator-initiated research grant from Baxter/Shire/Baxalta/Takeda (grant number GHOL 6238). This Article is written on behalf of the international multicentre OPTI-CLOT and To WiN studies that aim to implement a pharmacokinetic-guided approach for the treatment of bleeding disorders using population pharmacokinetic models for desmopressin, factor concentrates, and other alternative drugs. A complete list of the members of the OPTI-CLOT research programme is in the appendix (p 3) . We thank all patients and family members who participated in this trial. We also thank all haemophilia teams, nurses, and research coordinators for their indispensable assistance. Furthermore, we thank D Nieboer for his statistical advice, I van Vliet for trial support, and J M Heijdra and L M Schütte for their help and assistance during the trial period. Funding Information: REGS has received research support from Bayer, Baxalta, CSL Behring, Novo Nordisk, Pfizer, Sobi, and Sanquin. FJMvdM has received grants from Bayer, CSL Behring, Novo Nordisk, Octapharma, Pfizer, Roche, Takeda, and Sobi for the development of a registry of Hemophilia patients in the Netherlands (HemoNED). KF has received unrestricted research grants from CSL Behring, Sobi, and Novo Nordisk, and her institution has received consultancy fees from Grifols, Takeda, Novo Nordisk, and Roche. MC has received research grants from Bayer, CSL Behring, Roche, UniQure, and Novo Nordisk. FWGL has received unrestricted research grants from CSL Behring, Shire/Takeda, Sobi, and UniQure; is a consultant for UniQure, Novo Nordisk, Biomarin and Shire, from which the fees go to their institution; has received travel support from Sobi; and is a member of the data safety and monitoring board for a study sponsored by Roche. KM has received research support from Bayer and Alexion and consulting fees from UniQure, from which all fees go to their institution. RAAM has served as an advisor for Bayer, CSL Behring, Merck Sharp & Dohme, Shire, and Zeria, with all honoraria and fees paid to their department at their institution), and has received unrestricted research grants from Bayer, CSL Behring, and Shire. MHC has received grants from the governmental research institutes Dutch Research Institute (NWO), ZonMW, Innovation fund, NWO-NWA; unrestricted investigator-initiated research grants and educational and travel funding from Pfizer, Baxter/Baxalta/Shire, Bayer Schering Pharma, CSL Behring, Sobi Biogen, Novo Nordisk, Novartis, and Nordic Pharma; and has served as a member on steering boards of Roche, Novartis, and Bayer, with all grants, awards, and fees received going to their institution. JGvdB has received funding for educational activities from Bayer and Novo Nordisk. IvM has received research grants from Sobi and CSL Behring. All other authors declare no competing interests. Publisher Copyright: © 2021 Elsevier Ltd

PY - 2021/7

Y1 - 2021/7

N2 - Background: Dosing of replacement therapy with factor VIII concentrate in patients with haemophilia A in the perioperative setting is challenging. Underdosing and overdosing of factor VIII concentrate should be avoided to minimise risk of perioperative bleeding and treatment costs. We hypothesised that dosing of factor VIII concentrate on the basis of a patient's pharmacokinetic profile instead of bodyweight, which is standard treatment, would reduce factor VIII consumption and improve the accuracy of attained factor VIII levels. Methods: In this open-label, multicentre, randomised, controlled trial (OPTI-CLOT), patients were recruited from nine centres in Rotterdam, Groningen, Utrecht, Nijmegen, The Hague, Leiden, Amsterdam, Eindhoven, and Maastricht in The Netherlands. Eligible patients were aged 12 years or older with severe or moderate haemophilia A (severe haemophilia was defined as factor VIII concentrations of <0·01 IU/mL, and moderate haemophilia as 0·01–0·05 IU/mL), without factor VIII inhibitors, and planned for elective low or medium risk surgery as defined by surgical risk score. Patients were randomly assigned (1:1) using a web-based randomisation system and treatment minimisation, stratified by method of administration of factor VIII concentrate (continuous infusion vs bolus administration) and risk level of surgery (low and medium risk surgery), to the pharmacokinetic-guided or standard treatment group. The primary endpoint was total amount of infused factor VIII concentrate (IU per kg bodyweight) during perioperative period (from day of surgery up to 14 days after surgery). Analysis was by intention to treat and the safety analysis population comprised all participants who underwent surgery with factor VIII concentrate. This study is registered with the Netherlands Trial Registry, NL3955, and is now closed to accrual. Findings: Between May 1, 2014, and March 1, 2020, 98 patients were assessed for eligibility and 66 were enrolled in the trial and randomly assigned to the pharmacokinetic-guided treatment group (34 [52%]) or the standard treatment group (32 [48%]). Median age was 49·1 years (IQR 35·0 to 62·1) and all participants were male. No difference was seen in consumption of factor VIII concentrate during the perioperative period between groups (mean consumption of 365 IU/kg [SD 202] in pharmacokinetic-guided treatment group vs 379 IU/kg [202] in standard treatment group; adjusted difference −6 IU/kg [95% CI −88 to 100]). Postoperative bleeding occurred in six (18%) of 34 patients in the pharmacokinetic-guided treatment group and three (9%) of 32 in the standard treatment group. One grade 4 postoperative bleeding event occurred, which was in one (3%) patient in the standard treatment group. No treatment-related deaths occurred. Interpretation: Although perioperative pharmacokinetic-guided dosing is safe, it leads to similar perioperative factor VIII consumption when compared with standard treatment. However, pharmacokinetic-guided dosing showed an improvement in obtaining factor VIII concentrations within the desired perioperative factor VIII range. These findings provide support to further investigation of pharmacokinetic-guided dosing in perioperative haemophilia care. Funding: Dutch Research Council (NWO)-ZonMw and Takeda.

AB - Background: Dosing of replacement therapy with factor VIII concentrate in patients with haemophilia A in the perioperative setting is challenging. Underdosing and overdosing of factor VIII concentrate should be avoided to minimise risk of perioperative bleeding and treatment costs. We hypothesised that dosing of factor VIII concentrate on the basis of a patient's pharmacokinetic profile instead of bodyweight, which is standard treatment, would reduce factor VIII consumption and improve the accuracy of attained factor VIII levels. Methods: In this open-label, multicentre, randomised, controlled trial (OPTI-CLOT), patients were recruited from nine centres in Rotterdam, Groningen, Utrecht, Nijmegen, The Hague, Leiden, Amsterdam, Eindhoven, and Maastricht in The Netherlands. Eligible patients were aged 12 years or older with severe or moderate haemophilia A (severe haemophilia was defined as factor VIII concentrations of <0·01 IU/mL, and moderate haemophilia as 0·01–0·05 IU/mL), without factor VIII inhibitors, and planned for elective low or medium risk surgery as defined by surgical risk score. Patients were randomly assigned (1:1) using a web-based randomisation system and treatment minimisation, stratified by method of administration of factor VIII concentrate (continuous infusion vs bolus administration) and risk level of surgery (low and medium risk surgery), to the pharmacokinetic-guided or standard treatment group. The primary endpoint was total amount of infused factor VIII concentrate (IU per kg bodyweight) during perioperative period (from day of surgery up to 14 days after surgery). Analysis was by intention to treat and the safety analysis population comprised all participants who underwent surgery with factor VIII concentrate. This study is registered with the Netherlands Trial Registry, NL3955, and is now closed to accrual. Findings: Between May 1, 2014, and March 1, 2020, 98 patients were assessed for eligibility and 66 were enrolled in the trial and randomly assigned to the pharmacokinetic-guided treatment group (34 [52%]) or the standard treatment group (32 [48%]). Median age was 49·1 years (IQR 35·0 to 62·1) and all participants were male. No difference was seen in consumption of factor VIII concentrate during the perioperative period between groups (mean consumption of 365 IU/kg [SD 202] in pharmacokinetic-guided treatment group vs 379 IU/kg [202] in standard treatment group; adjusted difference −6 IU/kg [95% CI −88 to 100]). Postoperative bleeding occurred in six (18%) of 34 patients in the pharmacokinetic-guided treatment group and three (9%) of 32 in the standard treatment group. One grade 4 postoperative bleeding event occurred, which was in one (3%) patient in the standard treatment group. No treatment-related deaths occurred. Interpretation: Although perioperative pharmacokinetic-guided dosing is safe, it leads to similar perioperative factor VIII consumption when compared with standard treatment. However, pharmacokinetic-guided dosing showed an improvement in obtaining factor VIII concentrations within the desired perioperative factor VIII range. These findings provide support to further investigation of pharmacokinetic-guided dosing in perioperative haemophilia care. Funding: Dutch Research Council (NWO)-ZonMw and Takeda.

UR - http://www.scopus.com/inward/record.url?scp=85108329665&partnerID=8YFLogxK

U2 - 10.1016/S2352-3026(21)00135-6

DO - 10.1016/S2352-3026(21)00135-6

M3 - Article

C2 - 34171280

AN - SCOPUS:85108329665

SN - 2352-3026

VL - 8

SP - e492-e502

JO - The Lancet Haematology

JF - The Lancet Haematology

IS - 7

ER -

Perioperative pharmacokinetic-guided factor VIII concentrate dosing in haemophilia (OPTI-CLOT trial): an open-label, multicentre, randomised, controlled trial

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