Transdermal clonidine in the treatment of severe hyperemesis. A pilot randomised control trial: CLONEMESI

Abstract

Objective To study the efficacy of transdermal clonidine in the treatment of severe refractory hyperemesis gravidarum (HG), the most severe illness of pregnancy.Design The study had a randomised, double -blind, placebo-controlled, cross-over design (RCT).Setting Single tertiary referral hospital after admission of patients.Sample Twelve women of gestational age 6-12 weeks and a major grade of HG clinical severity who were unresponsive to standard antiemetic treatment.Methods The patients were randomly treated with and without the active drug (5 mg patch) for two consecutive periods of 5 days. The patients were allocated to a random list to receive first placebo and then active drug or the other way round. Other antiemetic drugs were administered on a scheduled or as-needed basis. All patients received intravenous hydration and thiamine supplementation. Main outcome measures Pregnancy Unique Quantification of Emesis (PUQE) and visual analog scale (VAS) clinical scores,positive morning urine ketonuria, number of doses of standard antiemetic drugs required, and number of days off intravenous therapy were compared in the two periods.Results Transdermal clonidine led to a significantly greater improvement compared with placebo of the primary (PUQE score P = 0.026 CI 0.43-3.24; VAS score P = 0.010 CI 2.17-12.83) and secondary outcome measures. A reduction of blood pressure was reported for systolic 6 mmHg P = 0.01 and diastolic 3 mmHg P = 0.055.Conclusions This preliminary RCT demonstrates the efficacy of transdermal clonidine in the treatment of severe HG, leading to a significant reduction of symptoms and reducing the need for other supportive measures and medications.

Treatments for hyperemesis gravidarum and nausea and vomiting in pregnancy: a systematic review and economic assessment

“…13,41,57,60,[62][63][64]66,67,69,70,76,[80][81][82][83][85][86][87][88][89]91,93,94,[98][99][100][101][102][103][104][106][107][108]110,[112][113][114][115] Methods employed included random number tables, computer-generated sequence generation 61,63,64,[81][82][83]88,93,94,98,99,106,108,…”

“…57,60,61,63,64,66,67,73,76,78,[80][81][82][83][84][85]88,89,93,98,99,102,103,[105][106][107][108]112,118 Thirty studies did not provide sufficient information to allow a judgement of low or high risk and were therefore classed as unclear. 13,[41][42][43]58,59,62,65,[68][69][70][71]74,75,77,79,90,91,[94][95][96][97]100,…”

“…Of the included RCT studies, 32 were judged to have low risk of bias in relation to the blinding of participants and other personnel involved in the trial, 41,57,[59][60][61][62][63][64]67,71,72,74,79,[81][82][83][84][85]90,93,99,100,102,103,105,106,108,110,112,113,116,117 generally through the provision of medication in identical formats for both active and placebo. Sixteen studies were judged to have high risk of bias in this respect, for example due to clear differences in either the appearance, dosage rates or mode of delivery between intervention and placebo comparator, or as a result of evidence that the research staff involved were aware of allocation status.…”

“…13,41,42,61,62,64,67,70,71,74,81,83,88,96,[101][102][103]106,110,112 However, a substantial number (n = 44) were classed as unclear, due to lack of sufficient information in the paper to permit detailed assessment of whether or not an important risk of bias existed, or due to insufficient rationale or evidence that an identified problem had introduced serious levels of bias to the study. 43,[57][58][59][60]65,66,68,69,72,73,[75][76][77][78][79][80]82,84,85,87,[89][90][91][92][93][94][95][97]…”

“…One trial by Maina and colleagues 85 studied the efficacy of a 5-mg transdermal clonidine patch in the treatment of HG, in a double-blind, placebo-controlled, crossover RCT. Patients were classified at the severe end of the HG spectrum, with the trial judged as having a low risk of bias.…”