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A prospective interventional study of Japanese herbal medicine, Ninjin-Youei-To on preoperative anemia and fatigue, insomnia and anxiety in patients who receive gynecologic operation (Ninjin-Youei-To study)

Ninjin-Youei-To study (Ninjin-Youei-To study)

40

In the iron supplementation group, the mean age was 43.3 +- 9.0 years, BMI was 21.3 +- 2.4 kg/m2, and the treatment duration was 34.6 +- 24.1 days. There were 11 patients with benign disease (61%) and 7 patients with malignant disease (39%). 17 patients were non-menopausal and 5 received hormone therapy. In contrast, the NYT group had a mean age of 41.1 +- 8.3 years with a mean BMI of 22.6 +- 2.7 kg/m2. The treatment duration was 39.9 +- 20.3 days. There were 11 patients with benign disease (73%) while 4 patients had malignant disease (27%). All patients were non-menopausal and 3 received hormone therapy during the study period, respectively. There was no difference in the characteristics between the groups.

We invited patients aged >=20 years who were scheduled to undergo gynecological surgery and who had anemia of less than Hb 11 g/dl on preoperative blood sampling and were to receive iron supplementation to participate in this study, and obtained consent for a total of 40 cases. During the trial period, due to the world wide spread of a COVID-19 infection, the framework of the surgical schedule has been changed and the duration of intervention could not be guaranteed. Hence, after consultation with the Ethics Committee, we have changed the duration of intervention from 28 days to >= 10 days. A total of 40 patients were randomly assigned according to the allocation table, 21 cases to the iron supplementation group and 19 cases to the NYT group. There were 3 withdrawals of consent and 3 cases of less than 10 days of intervention in the iron supplementation group, and 3 withdrawals of consent and 1 case of deviation from eligibility criteria in the NYT group. The intention to treat analysis was performed as the main analysis, and 18 patients in the iron supplementation group and 15 patients in the NYT group were compared after excluding the withdrawn consent cases and the cases that deviated from the eligibility criteria. In the subgroup analysis, the primary endpoints were additionally evaluated in the iron supplementation group and the NYT group, in which the duration of intervention was >=28 days.

In the case 23, mild liver dysfunction was observed on 25/Nov/2020. We immediately stop the medication. Subsequently, we confirmed recovery from the condition on 30/Nov/2020.

Efficacy endpoints Primary outcomes Hb value: The Hb value in the iron supplementation group was 10.0 +- 0.8 g/dl before treatment while 11.6 +- 1.6 g/dl and that in the NYT group was 9.8 +- 1.0 g/dl before treatment while 12.0 +- 1.0 g/dl after treatment. An inter-group comparison showed no statistically significant difference in the amount of change (P=0.29). Subgroup analysis showed similar results (P=0.82). Fatigue: The CFS score in the iron supplementation group was physical fatigue of 5.6 +- 4.7, mental fatigue of 6.9 +- 3.0, cognitive fatigue of 3.3 +- 3.5, and overall fatigue of 15.8 +- 8.5 before intervention while physical fatigue of 3.9 +- 3.6, mental fatigue of 6.9 +- 2.7, cognitive fatigue of 1.9 +- 2.3, and overall fatigue of 12.8 +- 6.2 after intervention and those in the NYT group was 7.1 +- 5.4 for physical fatigue, 7.9 +- 4.1 for mental fatigue, 2.8 +- 2.8 for cognitive fatigue, and 17.9 +- 10.2 for overall fatigue before intervention while 2.5 +- 2.4 for physical fatigue, 4.9 +- 3.4 for mental fatigue, 0.7 +- 1.0 for cognitive fatigue, and 8.1 +- 1.0 for overall fatigue after intervention. An inter-group comparison showed statistically significant difference in the amount of change in all items except for cognitive fatigue (physical fatigue, P=0.0154; mental fatigue, P=0.0308; cognitive fatigue, 0.1227; overall fatigue, P=0.006). Subgroup analysis showed that the respective changes were physical fatigue -3.0 +- 4.1, mental fatigue -0.33 +- 1.9, cognitive fatigue -2.6 +- 3.9, and overall fatigue -5.9 +- 8.2 in the iron supplementation group, and physical fatigue -4.0 +- 3.6, mental fatigue -2.5 +- 4.2, cognitive fatigue -1.7 +- 2.5, and overall fatigue -8.3 +- 6.4. in the NYT group. There were no statistically significant differences in any of these scores (P=0.42, P=0.2, P=0.87, P=0.36, respectively). Anxiety: The median VAS was 48 (interquartile range; 8, 66) before the intervention in the iron supplementation group and 31 (interquartile range; 9, 60) after the intervention. In contrast, the NYT group had a median VAS of 56 (interquartile range; 50, 70) before intervention and 23 (interquartile range; 6, 48) after intervention. A statistically significant difference was found between the two groups (P=0.0051). Subgroup analysis showed similar results (P=0.0331). Secondary outcomes Multiple regression analysis was not performed because there was no difference in the characteristics between the iron supplementation group and the NYT group. In an intra-group comparison of anemia (Hb), the Hb value in the iron supplementation group was 10.0 +- 0.8 g/dl before treatment while 11.6 +- 1.6 g/dl, with significant difference (P=0.0007). Moreover, that in the NYT group was9.8 +- 1.0 g/dl before treatment while 12.0 +- 1.0 g/dl after treatment, with significant difference (P<0.0001). In an intra-group comparison of fatigue (CFS), the CFS score in the iron supplementation group was physical fatigue of 5.6 +- 4.7, mental fatigue of 6.9 +- 3.0, cognitive fatigue of 3.3 +- 3.5, and overall fatigue of 15.8 +- 8.5 before intervention while physical fatigue of 3.9 +- 3.6, mental fatigue of 6.9 +- 2.7, cognitive fatigue of 1.9 +- 2.3, and overall fatigue of 12.8 +- 6.2 after intervention. There was no significant difference in any of the items (P=0.064, P=0.89, P=0.083, and P=0.07, respectively). On the other hand, those in the NYT group was 7.1 +- 5.4 for physical fatigue, 7.9 +- 4.1 for mental fatigue, 2.8 +- 2.8 for cognitive fatigue, and 17.9 +- 10.2 for overall fatigue before intervention while 2.5 +- 2.4 for physical fatigue, 4.9 +- 3.4 for mental fatigue, 0.7 +- 1.0 for cognitive fatigue, and 8.1 +- 1.0 for overall fatigue after intervention, with significant difference in all items (P = 0.0008, P = 0.017, P = 0.0093, and P = 0.0004, respectively). In an intra-group comparison of anxiety (VAS), the VAS score in the iron supplementation group was a median of 48 (interquartile range; 8, 66) before intervention while a median of 31 (interquartile range; 9, 60) after intervention, with no significant change (P = 0.2). On the other hand, those in the NYT group was a median of 56 (interquartile range; 50, 70) before intervention while a median of 23 (interquartile range; 6, 48) after intervention, indicating a significant decrease (P=0.0008). There was no difference in the amount of change in RBC, Platelet, Ht, Ferritin, Fe, UTBC, TIBC and PSQI. Safety endpoints We found one patient who had developed mild liver dysfunction in the present study. We immediately stopped the medication, subsequently, we confirmed the patient recovered quickly afterwards. In a previous report, 25 cases (3.1%) of 808 patients treated with NYT showed complications, most of which were gastrointestinal ones and no liver dysfunction was observed. Hence, the incidence was considered to be extremely low.

The combined use of NYT and iron supplementation for anemia before surgery for gynecological diseases improved patients' anemia as much as iron supplementation alone. Moreover, the combination therapy significantly alleviated their fatigue and anxiety. Thus, this combination therapy can be an effective treatment option in gynecological care.

Nov. 28, 2022

No

No

https://jrct.niph.go.jp/latest-detail/jRCT1051190012

Kimura Tadashi

Osaka University Hospital

2-15 Yamadaoka Suita city Osaka, Japan

tadashi@gyne.med.osaka-u.ac.jp

Yagi Taro

Osaka University Hospital

2-15 Yamadaoka Suita city Osaka, Japan

+81-6-6879-3351

yagit@gyne.med.osaka-u.ac.jp

Complete

Oct. 13, 2017

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

Patients who receive gynecologic operation and take Ferromia by diagnosing as anemia (Hb less than 11g/dl)
They subject with age more than 20 years

1. Patients with concomitant use of other Japanese herbal medicine
2. Patients with use of Japanese herbal medicine for fatigue, insomnia and anxiety within two weeks
3. Patients with depression
4. Patients with aldosteronism, myopathy and hypokalemia
5. Patients with liver dysfunction(AST more than 80 IU/L or ALT more than 80 IU/L)
6. Patients who are inappropriate to participate in the study

Female

anemia

Arm Ninjin-Youei-To: oral Ninjin-Youei-To 7.5mg per a day and oral Ferromia 50mg twice a day for 10 days or more until the admission date.
Arm Ferromia: oral Ferromia 50mg twice a day for 10 days or more until the admission date.

anemia

Hb, fatigue and anxiety

RBC, Platelet, Ht, Ferritin, Fe, TIBC, UIBC and insomnia

+81-6-6210-8324

none