Table 1.
General characteristics of included studies
| First author | Publish Year | Trial Phase | Trail No. | Funded | Country | Risk for PPH | Delivery Mode | Interventions (sample size; dose; adm) | Side effects |
|---|---|---|---|---|---|---|---|---|---|
| Mannaerts D [56] | 2018 | NA | ISRCTN95504420 | NA | Belgium | L | CS | Oxytocin (26; 20 iu, i.v.) vs. Carbetocin (32; 100 ug, i.v.) | Nausea |
| Flushing | |||||||||
| Hypotension | |||||||||
| Vomiting | |||||||||
| Taheripanah R [11] | 2018 | II | NCT02079558 | Shahid Beheshti University of Medical Sciences | Iran | H | CS | Oxytocin (110; 30 iu, i.v.) vs. Carbetocin (110; 100 ug, i.v.) | Vomiting |
| Headache | |||||||||
| Nausea | |||||||||
| Tremor | |||||||||
| Dizziness | |||||||||
| Pruritus | |||||||||
| Widmer M [12] | 2018 | III | Australian New Zealand Clinical Trials Registry number, ACTRN12614000870651; EudraCT number, 2014-004445-26; and Clinical Trials Registry-India number, CTRI/2016/05/006969 | Merch Sharpe & Dohme | Argentina; Egypt; India; Kenya; Nigeria; Singapore; South Africa; Thailand; Uganda; the United Kingdom | L | VD | Oxytocin (14743; 10 iu, i.m.) vs. Carbetocin (14754; 100 ug, i.m.) | Chest pain |
| Flushing | |||||||||
| Abdominal pain | |||||||||
| Vomiting | |||||||||
| Shady NW [55] | 2017 | NA | NA | NA | Egypt | L | VD | Oxytocin (120; 10 iu, i.v.) vs. Misoprostol (120; 600 ug, oral) vs. Tranexamic acid + Misoprostol (120; 1000 mg + 600 ug, oral) | Vomiting |
| Nausea | |||||||||
| Diarrhea | |||||||||
| El Behery MM [57] | 2016 | NA | NA | NA | Egypt | H | CS | Oxytocin (90; 20 iu, i.v.) vs. Carbetocin (90; 100 ug, i.v.) | Headache |
| Nausea | |||||||||
| Vomiting | |||||||||
| Sweating | |||||||||
| Palpitation | |||||||||
| Fever | |||||||||
| Gavilanes P [18] | 2016 | NA | NA | NA | Ecuador | H | CS | Oxytocin (50; 10 iu, i.v.) vs. Misoprostol (50; 400 ug, s.l.) | Shivering |
| Nausea | |||||||||
| Vomiting | |||||||||
| Headache | |||||||||
| Maged AM [59] | 2016 | NA | NA | NA | Egypt | H | VD | Oxytocin (100; 100 ug, i.m.) vs. Carbetocin (100; 100 ug, i.m.) | Nausea |
| Vomiting | |||||||||
| Tachycardia | |||||||||
| Flushing | |||||||||
| Dizziness | |||||||||
| Headache | |||||||||
| Shivering | |||||||||
| Anemia | |||||||||
| Metallic taste | |||||||||
| Dyspnea | |||||||||
| Palpitations | |||||||||
| Itching | |||||||||
| Maged AM [58] | 2016 | III | NCT02304055 | Cairo University | Egypt | H | VD | Oxytocin (50; 5 iu, i.v.) vs. Carbetocin (50; 100 ug, i.v.) | Nausea |
| Vomiting | |||||||||
| Tachycardia | |||||||||
| Flushing | |||||||||
| Dizziness | |||||||||
| Headache | |||||||||
| Shivering | |||||||||
| Metallic taste | |||||||||
| Dyspnea | |||||||||
| Palpitations | |||||||||
| Itching | |||||||||
| Othman ER [20] | 2016 | II | NCT02562300 | Assiut University | Egypt | L | CS | Oxytocin (60; 20 iu, i.v.) vs. Misoprostol (60; 400 ug, sub) | Pyrexia |
| Shivering | |||||||||
| Vomiting | |||||||||
| Headache | |||||||||
| Metallic taste | |||||||||
| Giddiness | |||||||||
| Razali N [61] | 2016 | NA | ISRCTN18976822 | the University of Malaya | Malaysia | L | CS | Oxytocin (271; 10 iu, i.v.) vs. Carbetocin (276; 100 ug, i.v.) | Arrhythmias |
| Sunil Kumar KS [60] | 2016 | NA | NA | NA | India | L | VD | Oxytocin (100; 10 iu, i.m.) vs. Carbetocin (100; 125 ug, i.m.) | Nausea |
| Vomiting | |||||||||
| Shivering | |||||||||
| Diarrhea | |||||||||
| Fever | |||||||||
| Musa AO [19] | 2015 | NA | PACTR201407000825227 | University of Ilorin Teaching Hospital | Nigeria | L | VD | Oxytocin (100; 10 iu, i.m.) vs. Misoprostol (100; 600 ug, p.o.) | Nausea |
| Diarhea | |||||||||
| Shivering | |||||||||
| Pyrexia | |||||||||
| Pakniat H [21] | 2015 | II | NCT01571323 and ACTRN12612000095864 | Qazvin University Of Medical Sciences | Iran | L | CS | Oxytocin (50; 20 iu, i.v.) vs. Misoprostol (50; 400 ug, sub) | Nausea |
| Vomiting | |||||||||
| Dyspnea | |||||||||
| Shivering | |||||||||
| Fever | |||||||||
| Chest pain | |||||||||
| Priya GP [22] | 2015 | NA | NA | NA | India | L | VD | Oxytocin (250; 10 iu, i.m.) vs. Misoprostol (250; 400 ug, sub) | Nausea |
| Vomiting | |||||||||
| Diarrhea | |||||||||
| Fever | |||||||||
| Shivering | |||||||||
| Atukunda EC [23] | 2014 | III | NCT01866241 | the Father Bash Foundation and Divine Mercy Hospital scholarship awards to ECA | Uganda | HL | VD | Oxytocin (570; 10 iu, i.m.) vs. Misoprostol (570; 600 ug, s.l.) | Vomiting |
| Nausea | |||||||||
| Headache | |||||||||
| Fever | |||||||||
| Shivering | |||||||||
| Diarrhea | |||||||||
| Afterpains | |||||||||
| Ezeama CO [66] | 2014 | NA | Pan African Clinical Trial Registry: 201105000292708 | NA | Nigeria | HL | VD | Oxytocin (151; 10 iu, i.m.) vs. Ergometrine (149; 500 ug, i.m.) | Nausea |
| Vomiting | |||||||||
| Headache | |||||||||
| Hypertension | |||||||||
| Rajaei M [24] | 2014 | I | NCT01863706 | Hormozgan University of Medical Sciences | Iran | HL | VD | Oxytocin (200; 20 iu, i.v.) vs. Misoprostol (200; 400 ug, p.o.) | Hypotension |
| Fever | |||||||||
| Chills | |||||||||
| Tewatia R [25] | 2014 | NA | NA | NA | India | L | VD | Oxytocin (50; 10 iu, i.v.) vs. Misoprostol (50; 600 ug, s.l.) | Fever |
| Shivering | |||||||||
| Nausea | |||||||||
| Vomiting | |||||||||
| Diarrhea | |||||||||
| Fazel MR [26] | 2013 | NA | NA | Kashan University of Medical Sciences | Iran | H | CS | Oxytocin (50; 10 iu, i.v.) vs. Misoprostol (50; 400 ug, i.v.) | Nausea |
| Vomiting | |||||||||
| Shivering | |||||||||
| Hyperpyrexia | |||||||||
| Chest pain | |||||||||
| Mukta M [27] | 2013 | NA | NA | NA | India | HL | VD | Oxytocin (100; 10 iu, i.m.) vs. Misoprostol (100; 600 ug, p.o.) | Shivering |
| Pyrexia | |||||||||
| Abdominal pain | |||||||||
| Diarrhea | |||||||||
| Nausea | |||||||||
| Vomiting | |||||||||
| Rosseland LA [6] | 2013 | IV | NCT00977769 | Ferring Pharmaceutical | Norway | H | CS | Oxytocin (26; 5 iu, i.v.) vs. Carbetocin (25; 100 ug, i.v.) vs. placebo | Metallic taste |
| Xerostomia | |||||||||
| Nasal congestion | |||||||||
| Headache | |||||||||
| Flushing | |||||||||
| Palpitations | |||||||||
| Shortness of breath | |||||||||
| Chest pain | |||||||||
| Feeling of warmth | |||||||||
| Adanikin AI [28] | 2012 | NA | NA | NA | Nigeria | H | CS | Oxytocin (109; 20 iu, i.v.) vs. Misoprostol (109; 600 ug, rec) | Nausea |
| Vomiting | |||||||||
| Shivering | |||||||||
| Pyrexia | |||||||||
| Badejoko OO [29] | 2012 | NA | ERC/2009/03/04 | NA | Nigeria | HL | VD | Oxytocin (132; 20 iu, i.v.) vs. Misoprostol (132; 600 ug, rec) | Vomiting |
| Pyrexia | |||||||||
| Shivering | |||||||||
| Bellad MB [31] | 2012 | III | NCT01373359 | Jawaharlal Nehru Medical College | India | L | VD | Oxytocin (331; 10 iu, i.m.) vs. Misoprostol (321; 400 ug, s.l.) | Nausea |
| Vomiting | |||||||||
| Shivering | |||||||||
| Fever | |||||||||
| Chaudhuri P [30] | 2012 | NA | CTRI/2009/091/000672 | NA | India | L | VD | Oxytocin (265; 10 iu, i.m.) vs. Misoprostol (265; 400 ug, s.l.) | Shivering |
| Fever | |||||||||
| Vomiting | |||||||||
| Nausea | |||||||||
| Diarrhea | |||||||||
| Moertl MG [63] | 2011 | NA | EudraCT number: 2007-005498-78; NCT01277978 | Medical University of Graz | Austria | H | CS | Oxytocin (28; 5 iu, i.v.) vs. Carbetocin (28; 100 ug, i.v.) | Nausea |
| Flushing | |||||||||
| Headache | |||||||||
| Tachycardia | |||||||||
| Shortness of breath | |||||||||
| Feeling warm | |||||||||
| Owonikoko KM [32] | 2011 | NA | NA | NA | Nigeria | H | CS | Oxytocin (50; 20 iu, i.v.) vs. Misoprostol (50; 400 ug, s.l.) | Nausea |
| Vomiting | |||||||||
| Headache | |||||||||
| Shivering | |||||||||
| Hypotension | |||||||||
| Reyes OA [62] | 2011 | NA | NA | NA | Panama | H | VD | Oxytocin (29; 20 iu, i.v.) vs. Carbetocin (26; 100 ug, i.v.) | Headaches |
| Palpitations | |||||||||
| Fever | |||||||||
| Nausea | |||||||||
| Vomiting | |||||||||
| Hot sensation | |||||||||
| Flushing | |||||||||
| Malaise | |||||||||
| Shrestha A [33] | 2011 | NA | NA | NA | Nepal | L | VD | Oxytocin (100; 10 iu, i.m.) vs. Misoprostol (100; 1000 ug, p.r.) | Shivering |
| Abdominal pain | |||||||||
| Afolabi EO [34] | 2010 | NA | NA | NA | Nigeria | Low | VD | Oxytocin (100; 10 iu, i.m.) vs. Misoprostol (100; 400 ug, p.o.) | Nausea |
| Shivering | |||||||||
| Attilakos G [17] | 2010 | NA | EudraCT number: 2005-002812-94 | Ferring UK funded the cost of preparation of the ‘blinded’drug ampoules | UK | High | CS | Oxytocin (189; 5 iu, i.v.) vs. Carbetocin (188; 100 ug, i.v.) | Nausea |
| Vomiting | |||||||||
| Headache | |||||||||
| Tachycardia | |||||||||
| Metallic taste | |||||||||
| Backache | |||||||||
| Abdominal pain | |||||||||
| Arm pain | |||||||||
| Trigeminy | |||||||||
| Flushed | |||||||||
| Shortness of breath | |||||||||
| Wheezing | |||||||||
| Tremors | |||||||||
| Hypotension | |||||||||
| Sweating | |||||||||
| Tightness throat | |||||||||
| ST depression | |||||||||
| Blurred vision | |||||||||
| Blum J [35] | 2010 | NA | NCT00116350 | The Bill & Melinda Gates Foundation | Burkina Faso; Egypt; Turkey; Vietnam | L | CS | Oxytocin (402; 40 iu, i.v.) vs. Misoprostol (407; 800 ug, sub) | Vomiting |
| Nausea | |||||||||
| Shivering | |||||||||
| Fever | |||||||||
| Dizziness | |||||||||
| Diarrhoea | |||||||||
| Butwick AJ [71] | 2010 | NA | NA | Stanford University School of Medicine | USA | H | CS | Oxytocin (15, 15, 14, 15; 0.5 iu, 1 iu, 3 iu, 5 iu, i.v.) vs. placebo | Hypotension |
| Tachycardia | |||||||||
| Nausea | |||||||||
| Chaudhuri P [36] | 2010 | NA | CTRI/2009/091/000075 | NA | India | H | CS | Oxytocin (94; 40 iu, i.v.) vs. Misoprostol (96; 800 ug, p.r.) | Shivering |
| Pyrexia | |||||||||
| Vomiting | |||||||||
| Winikoff B [37] | 2010 | NA | NCT00116350 | the Bill & Melinda Gates Foundation | Ecuador, Egypt, Vietnam | L | VD | Oxytocin (490; 40 iu, i.v.) vs. Misoprostol (488; 800 ug, sub) | Vomiting |
| Nausea | |||||||||
| Shivering | |||||||||
| Fever | |||||||||
| Fainting | |||||||||
| Diarrhoea | |||||||||
| Borruto F [64] | 2009 | NA | NA | NA | Italy | H | CS | Oxytocin (52; 10 iu, i.v.) vs. Carbetocin (52; 100 ug, i.v.) | Anemia |
| Arrhythmias | |||||||||
| Abdominal pain | |||||||||
| Nausea | |||||||||
| Vomiting | |||||||||
| Metallic taste | |||||||||
| Heat sensation | |||||||||
| Back pain | |||||||||
| Headache | |||||||||
| Tremor | |||||||||
| Dizziness | |||||||||
| Difficulty in breathing | |||||||||
| Dyspnea | |||||||||
| Chest pain | |||||||||
| Pruritus | |||||||||
| Flushing | |||||||||
| Hypotension | |||||||||
| Nasr A [38] | 2009 | NA | NA | NA | Egypt | L | VD | Oxytocin (257; 5 iu, i.m.) vs. Misoprostol (257; 800 ug, p.o.) | Nausea |
| Vomiting | |||||||||
| Diarrhea | |||||||||
| Shivering | |||||||||
| Fever | |||||||||
| Singh G [72] | 2009 | NA | NA | NA | India | L | VD | Oxytocin (75; 5 iu, i.v.) vs. Misoprostol (75, 75; 400 ug, 600 ug, s.l.) vs. Ergometrine (75; 200 ug, i.v.) | Fever |
| Shivering | |||||||||
| Orji E [67] | 2008 | NA | NA | NA | Nigeria | HL | VD | Oxytocin (297; 10 iu, i.v.) vs. Ergometrine (303; 250 ug, i.v.) | Nausea |
| Vomiting | |||||||||
| Headaches | |||||||||
| Hypertension | |||||||||
| Baskett TF [39] | 2007 | NA | NA | Nova Scotia Health Research Foundation | Canada | HL | VD | Oxytocin (311; 5 iu, i.v.) vs. Misoprostol (311; 400 ug, p.o.) | Shivering |
| Fever | |||||||||
| Parsons SM [40] | 2007 | NA | NA | MaterCare International and the Canadian Foundation for Women’s Health | Ghana | HL | VD | Oxytocin (226; 10 iu, i.m.) vs. Misoprostol (224; 800 ug, p.r.) | Nausea |
| Vomiting | |||||||||
| Shivering | |||||||||
| Fever | |||||||||
| Hypertension | |||||||||
| Saito K [68] | 2007 | NA | NA | NA | Japan | L | VD | Oxytocin (156; 5 iu, i.m.) vs. Ergometrine (187; 200 ug, i.m.) | Nausea |
| Headache | |||||||||
| Dyspnea | |||||||||
| Hypertension | |||||||||
| Gupta B [41] | 2006 | NA | NA | NA | India | HL | VD | Oxytocin (100; 10 iu, i.m.) vs. Misoprostol (100; 600 ug, p.r.) | Shivering |
| Nausea | |||||||||
| Fever | |||||||||
| Parsons SM [42] | 2006 | NA | NA | Matercare International and the Society of Obstetricians and Gynaecologists of Canada | Ghana | HL | VD | Oxytocin (225; 10 iu, i.m.) vs. Misoprostol (225; 800 ug, p.o.) | Nausea |
| Vomiting | |||||||||
| Diarrhea | |||||||||
| Shivering | |||||||||
| Fever | |||||||||
| Hypertension | |||||||||
| Vimala N [43] | 2006 | NA | NA | Division of Reproductive Health and Nutrition, Indian Council of Medical Research (ICMR), New Delhi | India | H | CS | Oxytocin (50; 20 iu, i.v.) vs. Misoprostol (50; 400 ug, s.l.) | Pyrexia |
| Shivering | |||||||||
| Vomiting | |||||||||
| Headache | |||||||||
| Metallic taste | |||||||||
| Giddiness | |||||||||
| Zachariah ES [73] | 2006 | NA | NA | NA | India | HL | VD | Oxytocin (617; 10 iu, i.m.) vs. Misoprostol (730; 400 ug, p.o.) vs. Ergometrine (676; 2000 ug, i.v.) | Fever |
| Nausea | |||||||||
| Vomiting | |||||||||
| Shivering | |||||||||
| Diarrhea | |||||||||
| Headache | |||||||||
| Boucher M [16] | 2004 | NA | NA | NA | Canada | H | VD | Oxytocin (77; 10 iu, i.v.) vs. Carbetocin (83; 100 ug, i.m.) | Headache |
| Chills | |||||||||
| Abdominal pain | |||||||||
| Dizziness | |||||||||
| Tremor | |||||||||
| Vasodilatation | |||||||||
| Leukocytosis | |||||||||
| Nausea | |||||||||
| Vomiting | |||||||||
| Pruritis | |||||||||
| Caliskan E [44] | 2003 | NA | NA | NA | Turkey | HL | VD | Oxytocin (384; 10 iu, i.v.) vs. Misoprostol (388; 600 ug, p.o.) | Shivering |
| Vomiting | |||||||||
| Diarrhea | |||||||||
| Fever | |||||||||
| Oboro VO [45] | 2003 | NA | NA | NA | Nigeria | L | VD | Oxytocin (249; 10 iu, i.m.) vs. Misoprostol (247; 600 ug, p.o.) | Nausea |
| Vomiting | |||||||||
| Diarrhoea | |||||||||
| Dizziness | |||||||||
| Shivering | |||||||||
| Fever | |||||||||
| Calişkan E [47] | 2002 | NA | NA | NA | Turkey | HL | VD | Oxytocin (407; 10 iu, i.v.) vs. Misoprostol (396; 600 ug, p.r.) | Shivering |
| Vomiting | |||||||||
| Diarrhea | |||||||||
| Fever | |||||||||
| Karkanis SG [46] | 2002 | NA | NA | The Physicians Services Incorporated Foundation | Canada | L | VD | Oxytocin (110; 10 iu, i.m.) vs. Misoprostol (105; 400 ug, p.r.) | Nausea |
| Vomiting | |||||||||
| Headache | |||||||||
| Shivering | |||||||||
| Abdominal pain | |||||||||
| Fever | |||||||||
| Acharya G [48] | 2001 | NA | NA | NA | UK | High | CS | Oxytocin (30; 10 iu, i.v.) vs. Misoprostol (30; 400 ug, p.o.) | Vomiting |
| Headache | |||||||||
| Bugalho A [49] | 2001 | NA | NA | Maputo Central Hospital and the Special Program on Research and Research Training in Human Reproduction of WHO | Mozambique | HL | VD | Oxytocin (339; 10 iu, i.m.) vs. Misoprostol (324; 400 ug, p.r.) | Vomiting |
| Diarrhea | |||||||||
| Shivering | |||||||||
| Gerstenfeld TS [50] | 2001 | NA | NA | NA | USA | HL | VD | Oxytocin (166; 20 iu, i.v.) vs. Misoprostol (159; 400 ug, p.r.) | Shivering |
| Gülmezoglu AM [51] | 2001 | NA | NA | UNDP/UNFPA/WHO/World Bank Special Programme of Research | Argentina; China; Egypt; Ireland; Nigeria; South Africa; Switzerland; Thailand; Vietnam | HL | VD | Oxytocin (9266; 10 iu, i.v./i.m.) vs. Misoprostol (9264; 600 ug, p.o.) | Shivering |
| Fever | |||||||||
| Nausea | |||||||||
| Vomiting | |||||||||
| Diarrhoea | |||||||||
| Kundodyiwa TW [52] | 2001 | NA | NA | NA | Zimbabwe | L | VD | Oxytocin (256; 10 iu, i.m.) vs. Misoprostol (243; 400 ug, p.o) | Shivering |
| Vomiting | |||||||||
| Nausea | |||||||||
| Diarrhea | |||||||||
| Fever | |||||||||
| Hypertension | |||||||||
| Lokugamage AU [53] | 2001 | NA | NA | NA | UK | H | CS | Oxytocin (20; 10 iu, i.v.) vs. Misoprostol (20; 500 ug, p.o.) | Shivering |
| Walley RL [54] | 2000 | NA | NA | MaterCare International and the Canadian International Development Agency | Ghana | L | VD | Oxytocin (198; 10 iu, i.m.) vs. Misoprostol (203; 400 ug, p.o.) | Nausea |
| Vomiting | |||||||||
| Diarrhoea | |||||||||
| Shivering | |||||||||
| Fever | |||||||||
| Dansereau J [65] | 1999 | NA | NA | A Clinical Research Grant from Ferring Inc., Canada | Canada | H | CS | Oxytocin (330; 25 iu, i.v.) vs. Carbetocin (329; 100 ug, i.v.) | Abdominal pain |
| Back pain | |||||||||
| Headache | |||||||||
| Nausea | |||||||||
| Metallic taste | |||||||||
| Flushing | |||||||||
| Sweating | |||||||||
| Tremors | |||||||||
| Vomiting | |||||||||
| Feeling of warmth | |||||||||
| Chou MM [70] | 1994 | NA | NA | Tachung Veterans General Hospital | China | HL | CS | Oxytocin (30; 20 iu, i.v.) vs. Prostaglandin (30; 125 ug, i.m.) | Vomiting |
| Diarrhea | |||||||||
| Flushing | |||||||||
| Dizziness | |||||||||
| Pyrexia | |||||||||
| Moir DD [69] | 1979 | NA | NA | NA | UK | L | VD | Oxytocin (44; 10 iu, i.v.) vs. Ergometrine (44; 500 ug, i.v.) | Vomiting |
CS: cesarean section; H: high risk for PPH; HL: high and low risk for PPH; L: low risk for PPH; NA: none; PPH: postpartum hemorrhage; VD: vaginal birth.