Overlapping approach Proton Pump Inhibitors/Nux vomica-Heel as new intervention for gastro-esophageal reflux management: Delphi consensus study

Table 1 Characteristics and actions of the medication object of the Delphi consensus, Nux vomica-Heel

Characteristics of Nux vomica-Heel
Nux vomica-Heel tablets (also marketed as Gastricumeel®, Biologische Heilmittel Heel GmbH, Baden-Baden - Germany) is a natural, multicomponent low dose medication consisting of six ingredients from the homeopathic tradition useful for the treatment of bloating, acid reflux, and other symptoms as well as for heartburn
Each component of Nux vomica-Heel, according to literature (basic research), exerts a cohort of function
Nux vomica: Modulation of acid secretion[16-19]
Pulsatilla: Modulation of mucosal inflammation; modulation of mucosal secretions[21]
Antimonium crudum: Modulation of mucosal inflammation[22,23]
Argentum nitricum: Modulation of mucosal inflammation; increased EGF (Epidermal Growth Factor) release[24,25]
Arsenicum album: Modulation of mucosal inflammation; reduced VEGF (Vasal Endothelial Growth Factor) release[26,27]
Carbo vegetabilis: Chelation of toxins[28,29]
According to the composition, three can be the main actions of Nux vomica-Heel:
(1) Aetiologic, through a direct modulation of acid secretion
(2) Symptomatic, through the modulation of gastric mucosa acute inflammation
(3) Preventive, through the modulation of gastric mucosa inflammation progression

Table 2 Synoptic table of the correlation between components of Nux vomica-Heel and keywords from traditional use

Keywords	Components of Nux vomica-Heel
	Nux vomica	Argentum nitricum	Arsenicum album	Pulsatilla	Antimonium crudum	Carbo vegetabilis
Mucosal inflammation		X	X		X
Gastric pyrosis	X	X	X			X
Abdominal distension		X			X	X
Abdominal pain				X
Abdominal colic				X
Chelating action on toxins						X
Alcoholic gastritis	X	X
Epigastric pain						X
Gastrodynia	X

“X” symbol is used to mark the match between orizzontally listed componets and vertically listed traditional fields of application.

Table 3 Statements

Topic A: GERD disease

(1) The epidemiological and socio-economic impact of GERD is very high

(2) GERD is diagnosed in the presence of typical symptoms (heartburn and/or regurgitation and/or retrosternal pain)

(3) The presence of only atypical symptoms (chest pain, cough, asthma, hoarseness, frequent throat clearing) without the co-presence of typical symptoms, would not be suggestive for GERD diagnosis

(4) Based on the symptoms, GERD can be diagnosed, and the treatment be prescribed by GPs, Otolaryngologists, and Geriatricians other than Gastroenterologists

Topic B: GERD treatment

(5) The most common management strategy for GERD targets heartburn reduction and inducing repair of the inflamed mucosa

(6) In case of GERD, PPIs are the most prescribed drugs for GERD symptoms resolution

(7) The most common adverse effects associated with PPIs are SIBO, gastrointestinal infections, malabsorption, osteoporosis, and neoplasia

(8) The main issue in the clinical management of patients affected by GERD is the symptoms rebound when the PPI therapy is discontinued

(9) PPIs deprescription is advisable when alternative therapies are available

(10) The natural low dose multicomponent medication Nux vomica-Heel is effective in the management of patients affected by acid-related disorders

(11) The prescription of Nux vomica-Heel in patients affected by acid-related disorders is desirable also in light of its high safety and tolerability profile

(12) In patients under long-term treatment with PPI, to clinically manage GERD symptoms, the administration of Nux vomica-Heel in overlapping with the PPI is recommended to reduce and suspend the use of the PPI

(13) In patients presenting GERD symptoms, the use of Nux vomica-Heel can be recommended as maintenance therapy after discontinuing the PPI

(14) In patients who presented GERD symptoms, after remission obtained with PPIs, LDA and symptoms remission can be maintained by a long-term administration of Nux vomica-Heel, 1 tablet sublingually 3 times per day far from meals (as needed 1 tablet every 15 min for no more than 2 h)

(15) In patients under long-term treatment with PPI, the overlapping directions for Nux vomica-Heel and PPI (for the PPI discontinuation) are the following:

First two weeks: PPI at the recommended dose according to the dosage schedule plus Nux vomica-Heel 1 tablet sublingually 3 times a day far from meals (as needed 1 tablet every 15 min for no more than 2 h)

Third week: PPI at the recommended dose according to the dosing schedule on alternate days plus Nux vomica-Heel 1 tablet sublingually 3 times a day far from meals (as needed 1 tablet every 15 min for no more than 2 h)

Fourth week: PPI at the recommended dose according to the dosing scheme two days a week plus Nux vomica-Heel 1 tablet sublingually 3 times a day far from meals (as needed 1 tablet every 15 min for no more than 2 h)

From the fifth week: Nux vomica-Heel 1 tablet sublingually 3 times a day far from meals (as needed 1 tablet every 15 min for no more than 2 h). PPI as needed

GERD: Gastro-esophageal reflux disease; PPIs: Proton Pump Inhibitors; SIBO: Small Intestine Bacterial Overgrowth; LDA: Low Disease Activity; GPs: General Practitioners.

Table 4 Voting results agreement for each individual statement in the Delphi consensus

	(1) Strongly disagree	(2) Disagree	(3) Undecided	(4) Agree	(5) Strongly agree	Sum votes 4-5	1st round consensus (reached if % greater than 66%)	2nd round consensus (reached if % greater than 66%)
Topic A: GERD disease
Statement 1 1st round	0/49	1/49	3/49	28/49	17/49	45	92
Statement 2 1st round	1/49	3/49	3/49	35/49	7/49	42	86
Statement 3 1st round	1/49	16/49	6/49	23/49	3/49	26	53
Statement 3 2nd round	3/40	9/40	0/40	26/40	2/40	28		70
Statement 4 1st round	1/49	2/49	1/49	25/49	20/49	45	92
Topic B: GERD treatment
Statement 5 1st round	0/49	2/49	3/49	36/49	8/49	44	90
Statement 6 1st round	0/49	1/49	1/49	39/49	8/49	47	96
Statement 7 1st round	0/49	2/49	2/49	30/49	15/49	45	92
Statement 8 1st round	0/49	1/49	3/49	32/49	13/49	45	92
Statement 9 1st round	1/49	1/49	1/49	30/49	16/49	46	94
Statement 10 1st round	0/49	0/49	2/49	36/49	11/49	47	96
Statement 11 1st round	0/49	0/49	0/49	30/49	19/49	49	100
Statement 12 1st round	0/49	1/49	3/49	33/49	12/49	45	92
Statement 13 1st round	0/49	0/49	0/49	33/49	16/49	49	100
Statement 14 1st round	0/49	1/49	2/49	32/49	14/49	46	94
Statement 15 1st round	0/49	2/49	2/49	35/49	10/49	45	92

GERD: Gastro-esophageal reflux disease.