Introduction and enrollment summary

This document provides an automated summary of data entered from ELICIT. It is generated from a dataset built from the MuSIC server and is updated weekly. These data lag the actual collected data by roughly two weeks (for the primary forms) and in some cases longer (e.g. for labs that have a longer turnaround time). Also, because data quality is being monitored, with corrections made and missing data added, there can be some variance in the data from day to day even if new subjects have not been added.

As of today, inital assessment data from 1205 children have been entered (this includes 17 children who were ultimately not eligible)

The number of children with initial assessment data entered by week since enrollment began is as follows:

Eligibility

Of the 17 children who were not eligible, 3 did not consent to participation, 7 expected to move from the study area, 1 had a mother with age < 18, 2 were from a multiple pregnancy, 2 children were not healthy at the time of assessment, 0 had a child weight less than 1.5kg, 2 children were older than 14 days of age, 0 were not eligible for other reasons, and 0 already had a child enrolled in ELICIT. Additionally, 86 children did not remain in the study. 13 of these were due to death.

This leaves 1102 children in the study at present.

Modified intention to treat vs per protocol

Of the 757 children who are 18 months or older, 757 have the outcome of interest measured. Of these, 644 meet the per protocol criteria (ie breastfed for 6 month, at least 50% of nicotinamide doses, all azithromycin doses, first doses of nitazoxinide, outcome of interest measure). When restricting the per protocol definition to include only antimicrobial doses received during the approved protocol window, 373 meet the definition.

Baseline characteristics by randomization arm

Group 1 (n = 281) Group 2 (n = 279) Group 3 (n = 275) Group 4 (n = 267)
child age (days) 6 +/- 3.4 5.8 +/- 3.7 5.9 +/- 3.6 6 +/- 3.7
# male sex (%) 147 (52.3%) 143 (51.3%) 142 (51.6%) 137 (51.3%)
# born in hospital (%) 155 (55.2%) 149 (53.4%) 132 (48%) 134 (50.2%)
Median family income med:30000 (min: 5000, max: 6e+05) med:30000 (min: 5000, max: 3e+05) med:30000 (min: 5000, max: 360000) med:30000 (min: 1500, max: 3e+05)
Mother with >= 7 years of education (%) 228/281 (81.1%) 197/279 (70.6%) 204/275 (74.2%) 198/267 (74.2%)
Birth order med:3 (min: 1 max: 12) med:4 (min: 1 max: 12) med:4 (min: 1 max: 12) med:3 (min: 1 max: 12)
# Iraqw 219/281 (77.9%) 229/279 (82.1%) 218/275 (79.3%) 216/267 (80.9%)
# w/ improved sanitation (%) 36/281 (12.8%) 23/279 (8.2%) 25/275 (9.1%) 33/267 (12.4%)
# w/ improved drinking water (%) 187/281 (66.5%) 182/279 (65.2%) 187/275 (68%) 175/267 (65.5%)
# treating water (%) 39/281 (13.9%) 27/279 (9.7%) 32/275 (11.6%) 27/267 (10.1%)
# w/ water > 10 minute walk away (%) 230/281 (81.9%) 223/279 (79.9%) 225/275 (81.8%) 212/267 (79.4%)
# w/ electricity (%) 100/281 (35.6%) 99/279 (35.5%) 90/275 (32.7%) 87/267 (32.6%)
# w/ mattress (%) 173/281 (61.6%) 153/279 (54.8%) 149/275 (54.2%) 151/267 (56.6%)
# w/ table (%) 138/281 (49.1%) 109/279 (39.1%) 107/275 (38.9%) 106/267 (39.7%)
# w/ bench (%) 245/281 (87.2%) 236/279 (84.6%) 224/275 (81.5%) 224/267 (83.9%)
# w/ separate kitchen (%) 183/281 (65.1%) 166/279 (59.5%) 173/275 (62.9%) 160/267 (59.9%)
# w/ refrigerator (%) 5/281 (1.8%) 2/279 (0.7%) 2/275 (0.7%) 5/267 (1.9%)
# w/ television (%) 18/281 (6.4%) 17/279 (6.1%) 20/275 (7.3%) 15/267 (5.6%)
# w/ mobile phone (%) 232/281 (82.6%) 237/279 (84.9%) 222/275 (80.7%) 223/267 (83.5%)
# w/ family bank account (%) 22/281 (7.8%) 19/279 (6.8%) 9/275 (3.3%) 13/267 (4.9%)
# own agricultural land (%) 269/281 (95.7%) 267/279 (95.7%) 266/275 (96.7%) 257/267 (96.3%)
maternal age (years) 28 +/- 7.1 27.8 +/- 6.7 27.8 +/- 6.1 27.7 +/- 6.6
enrollment length (cm) 49.2 +/- 2 min:42.2 max: 59 48.8 +/- 2.1 min:40 max: 57 49.1 +/- 2.1 min:41 max: 55 49.1 +/- 2.1 min:38 max: 57
enrollment weight (kg) 3.1 +/- 0.5 min:1.8 max: 4.6 3.1 +/- 0.5 min:1.9 max: 6.6 3.1 +/- 0.5 min:1.6 max: 4.4 3.2 +/- 0.5 min:1.6 max: 5.7
enrollment head circumference (cm) 34.7 +/- 1.3 min:31 max: 38.2 34.6 +/- 1.3 min:30 max: 38.4 34.8 +/- 1.4 min:28.3 max: 38.5 34.8 +/- 1.3 min:31.5 max: 40

Illness, healthcare accessed, and antibiotic use

####Healthcare accessed in last week by child age and nicotinamide assignment

####Healthcare accessed in last week by child age and antibiotic assignment

####Illness in the last week by child age and nicotinamide treatment assignment:

####Illness in the last week by child age and antibiotic treatment assignment:

####Antibiotic use in the last week by child age and nicotinamide treatment assignment:

####Antibiotic use in the last week by child age and antibiotic treatment assignment:

##Adverse events in mothers To date, there have been 465 adverse events in mothers (249 in NIC-A and 216 in NIC-B). There have been 26 serious adverse events(14 in NIC-A and 12 in NIC-B) and 0 adverse events deemed related or possibily related to study medications (0 in NIC-A and 0 in NIC-B).

####Serious adverse event categories in mothers by nicotinamide arm: Events may include multiple diagnoses

Diganosis Nic-A Nic-B
ALRI 2 3
diarrhea 3 2
DVT 1 0
Lab abnormality 2 3
Other 6 6
Sepsis 2 3
Injury/Burn/Bites 1 0
Septicemia 0 1
Ear infection 0 1

The “other” serious AEs for NIC-A were as follows: EPILEPSY, UNSPECIFIED GASTROINTESTINAL ILLNESS, ACUTE ASTHMATIC ATTACK, 1. UNSPECIFIED RESPIRATORY ILLNESS, UNSPECIFIED ILLNESS, 1. ANGINA PECTORIS.

The “other” serious AEs for NIC-B were as follows: POSTPARTUM PRE ECLAMPSIA, SCHIZOAFFECTIVE DISORDER, SUSPECTED ORGANOPHOSPHATE POISONING, SEIZURE DISORDER, 1. SUSPECTED ANGINA PECTORIS, UNSPECIFIED ILLNESS

Adverse events in children

###By Nicotinamide arm: To date, there have been 4349 adverse events in children (2179 in NIC-A and 2170 in NIC-B). There have been 264 serious adverse events(129 in NIC-A and 135 in NIC-B) and 0 adverse events deemed related or possibily related to study medications (0 in NIC-A and 0 in NIC-B).

Of the 13 that died, 7 were in Nic-A, and 6 were in Nic-B.

####Serious adeverse events by nicotinimide arm for children six months and younger An adverse events may include multiple diagnoses

Diagnosis Nic-A Nic-B
Acute watery diarrhea 3 4
ALRI 39 36
diarrhea 7 12
Jaundice 0 1
Lab abnormality 7 5
Malnutrition 2 0
Sepsis 8 12
Skin rash/infection 0 1
UTI 1 1

The “other” SAEs for NIC-A were as follows:

The “other” SAEs for NIC-B were as follows:

####Serious adverse events by nicotinamide arm for children older than six months An adverse events may include multiple diagnoses

Diganosis Nic-A Nic-B
Acute watery diarrhea 2 5
ALRI 39 38
diarrhea 47 37
Dysentery 0 1
fever 2 3
Injury/Burn/Bites 1 2
Lab abnormality 19 24
Malnutrition 5 4
Omphalitis 1 0
Other 5 4
Septicemia 1 3
Skin rash/infection 1 1
UTI 0 3

The “other” serious AEs for NIC-A were as follows: 1. CHICKEN POXS WITH BACTERIAL SUPERINFECTION, SCORPION BITE, ACUTE BACTERIAL MENINGITIS , UNSPECIFIED GASTROINTESTINAL ILLNESS, (1)UNSPECIFIED GASTROINTESTINAL ILLNESS(

The “other” serious AEs for NIC-B were as follows: 1. SUSPECTED BACTERIAL MENINGITIS , PNEOMONIA, UNSPECIFIED GASTROINTESTINAL ILLNESS, CHICKEN POX

###By antibiotic arm

To date, there have been 2800 adverse events in children 6 months and older, (1457 in ANTI-A and 1343 in ANTI-B). There have been 161 serious adverse events(85 in ANTI-A and 76 in ANTI-B) and 0 adverse events deemed related or possibily related to study medications (0 in ANTI-A and 0 in ANTI-B).

Of the 13 that died, 8 were in Anti-A, and 5 were in Anti-B.

####Serious adverse events for children older than 6 months An adverse events may include multiple diagnoses

Diganosis ANTI-A ANTI-B
Acute watery diarrhea 3 4
ALRI 42 35
diarrhea 42 42
Dysentery 1 0
fever 4 1
Injury/Burn/Bites 2 1
Lab abnormality 21 22
Malnutrition 6 3
Omphalitis 1 0
Other 4 5
Septicemia 2 2
Skin rash/infection 1 1
UTI 1 2

The “other” serious AEs for ANTI-A were as follows: 1. CHICKEN POXS WITH BACTERIAL SUPERINFECTION, SCORPION BITE, UNSPECIFIED GASTROINTESTINAL ILLNESS, (1)UNSPECIFIED GASTROINTESTINAL ILLNESS(

The “other” serious AEs fo ANTI-B were as follows: 1. SUSPECTED BACTERIAL MENINGITIS , PNEOMONIA, UNSPECIFIED GASTROINTESTINAL ILLNESS, CHICKEN POX, ACUTE BACTERIAL MENINGITIS

##By randomization arm

All serious adverse events for children older than 6 months An adverse events may include multiple diagnoses

Protocol deviations by nicotanmide arm

NIC-A NIC-B
Any protocol deviation 524 454
Inappropriate documentation of consent 0 1
Study medication given outside of time window 180 179
Study antimicrobials given prior to stool colelction 5 2
Incorrect does of study medication 5 6
Delay of AE/SAE reporting 7 14
Blood for safety labs at 2 months (first 100 participants) not obtained 326 252

Protocol deviations by antibiotic arm

ANTI-A ANTI-B
Any protocol deviation 490 488
Inappropriate documentation of consent 0 1
Study medication given outside of time window 185 174
Study antimicrobials given prior to stool colelction 4 3
Incorrect does of study medication 5 6
Delay of AE/SAE reporting 8 13
Blood for safety labs at 2 months (first 100 participants) not obtained 288 290

##Protocol deviations by study arm

1 2 3 4
Any protocol deviation 262 262 228 226
Inappropriate documentation of consent 0 0 0 1
Study medication given outside of time window 95 85 90 89
Study antimicrobials given prior to stool colelction 3 2 1 1
Incorrect does of study medication 1 4 4 2
Delay of AE/SAE reporting 1 6 7 7
Blood for safety labs at 2 months (first 100 participants) not obtained 162 164 126 126

Compliance with study medications

Objective nicotanimide pill/packet compliance (based on pill/packet counting performed every 2 months starting at the 2 month visit):

Subjective nicotanimide pill compliance (based on maternal report of pills consumed in the previous 7 days at each monthly visit):

Subjective nicotinimide packet compliance based on maternal report of the number of packets missed in the last 7 days

##Objective compliance vs subjective compliance

Subjective minority Subjective majority
Objective minority 104 951
Objective majority 287 7058

Breastfeeding status

####Prevalence of breastfeeding as primary source of food by child age in months and nicotinamide treatment assignment: